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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03284723
Registration number
NCT03284723
Ethics application status
Date submitted
1/09/2017
Date registered
15/09/2017
Date last updated
3/09/2024
Titles & IDs
Public title
PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors
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Scientific title
A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors
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Secondary ID [1]
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2017-002538-22
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Secondary ID [2]
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C0541001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms
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Condition category
Condition code
Cancer
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Breast
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - PF-06804103
Treatment: Drugs - PF-06804103 + Palbociclib +Letrozole
Experimental: PF-06804103 - Study Treatment
Experimental: PF-06804103+Combination Regimen - Study Treatment
Treatment: Drugs: PF-06804103
Dose Escalation Part - 1A Dose Expansion Part - 2A
Treatment: Drugs: PF-06804103 + Palbociclib +Letrozole
Dose Escalation - Part 1B Dose Expansion - Part 2B
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A
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Assessment method [1]
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A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose). (1) Hematologic: Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; thrombocytopenia; (2) Non-hematologic: Grade \>=3 toxicities that were considered clinically significant; delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting treatment related toxicities; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.
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Timepoint [1]
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First cycle, Day 1 up to Day 21
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Primary outcome [2]
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Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B
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Assessment method [2]
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A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 28 days of first dose). (1) Hematologic: including a delay greater than 1 week in administration of the next scheduled dose of study treatment due to persistent treatment-related toxicities; Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; thrombocytopenia. (2) Non-hematologic: including Grade \>=3 toxicities that are considered clinically significant; Grade 3 QTc prolongation despite correction of reversible causes; delayed by \>2 week in receiving the next scheduled dose of any study treatment due to persisting treatment-related toxicities; inability to administer at least 80% of the planned palbociclib or letrozole or 100% of the planned PF-06804103 doses during Cycle 1 due to toxicity related to the study treatment; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.
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Timepoint [2]
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First Cycle, Day 1 up to Day 28
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Primary outcome [3]
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Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs
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Assessment method [3]
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as those with initial onset or increasing in severity after the first dose of study medication. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.
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Timepoint [3]
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From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
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Primary outcome [4]
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Number of Participants With Laboratory Abnormalities-Hematology
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Assessment method [4]
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Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: anemia, INR increased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased.
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Timepoint [4]
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From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
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Primary outcome [5]
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Number of Participants With Laboratory Abnormalities-Chemistries
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Assessment method [5]
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Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, hyperglycemia, hypermagnesemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased.
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Timepoint [5]
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From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
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Primary outcome [6]
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Number of Participants With Laboratory Abnormalities-Urinalysis
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Assessment method [6]
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Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above.
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Timepoint [6]
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From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
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Primary outcome [7]
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Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria
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Assessment method [7]
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Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position.
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Timepoint [7]
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From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B
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Primary outcome [8]
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Percentage of Participants With Objective Response in Part 2
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Assessment method [8]
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Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
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Timepoint [8]
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Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
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Primary outcome [9]
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Duration of Response (DR) in Part 2
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Assessment method [9]
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Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [9]
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Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
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Primary outcome [10]
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Progression-Free Survival (PFS) in Part 2
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Assessment method [10]
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Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [10]
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Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
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Primary outcome [11]
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Time to Tumor Progression (TTP) in Part 2
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Assessment method [11]
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Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [11]
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Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks)
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Secondary outcome [1]
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Percentage of Participants With Objective Response in Part 1
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Assessment method [1]
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Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
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Timepoint [1]
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Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
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Secondary outcome [2]
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Duration of Response (DR) in Part 1
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Assessment method [2]
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0
Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [2]
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Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
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Secondary outcome [3]
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Progression-Free Survival (PFS) in Part 1
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Assessment method [3]
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0
Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [3]
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Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
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Secondary outcome [4]
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Time to Tumor Progression (TTP) in Part 1
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Assessment method [4]
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Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
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Timepoint [4]
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0
Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
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Secondary outcome [5]
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Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103
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Assessment method [5]
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To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06804103.
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Timepoint [5]
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Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
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Secondary outcome [6]
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Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis
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Assessment method [6]
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Tumor tissues from archived tissue biopsy were analyzed for HER2 mutations.
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Timepoint [6]
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Baseline
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Secondary outcome [7]
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Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC)
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Assessment method [7]
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Cmax is maximum observed serum concentration. Cmax for PF-06804103 ADC was observed directly from data. Part 2A used a sparse pharmacokinetic (PK) sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
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Timepoint [7]
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Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
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Secondary outcome [8]
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Terminal Serum Half-Life (t1/2) of PF-06804103 ADC
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Assessment method [8]
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Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [8]
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Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
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Secondary outcome [9]
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Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC
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Assessment method [9]
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AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [9]
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Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
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Secondary outcome [10]
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Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC
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Assessment method [10]
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Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 ADC was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [10]
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0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
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Secondary outcome [11]
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Clearance (CL) of PF-06804103 ADC
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Assessment method [11]
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0
Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 ADC was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [11]
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0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
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Secondary outcome [12]
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0
Volume of Distribution at Steady State (Vss) of PF-06804103 ADC
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Assessment method [12]
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [12]
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0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
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Secondary outcome [13]
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0
Observed Accumulation Ratio (Rac) of PF-06804103 ADC
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Assessment method [13]
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0
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [13]
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0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
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Secondary outcome [14]
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0
Cmax of PF-06804103 Total Antibody
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Assessment method [14]
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0
Cmax is maximum observed serum concentration. Cmax for PF-06804103 total antibody was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Total antibody means PF-06804103 with or without PF-06380101 conjugated. Both the antibody and small molecule components of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK.
Query!
Timepoint [14]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [15]
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0
t1/2 of PF-06804103 Total Antibody
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Assessment method [15]
0
0
Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [15]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [16]
0
0
AUCinf of PF-06804103 Total Antibody
Query!
Assessment method [16]
0
0
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [16]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
Query!
Secondary outcome [17]
0
0
AUCtau of PF-06804103 Total Antibody
Query!
Assessment method [17]
0
0
Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [17]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Query!
Secondary outcome [18]
0
0
CL of PF-06804103 Total Antibody
Query!
Assessment method [18]
0
0
Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 total antibody was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [18]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [19]
0
0
Vss of PF-06804103 Total Antibody
Query!
Assessment method [19]
0
0
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [19]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Query!
Secondary outcome [20]
0
0
Rac of PF-06804103 Total Antibody
Query!
Assessment method [20]
0
0
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [20]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Query!
Secondary outcome [21]
0
0
Cmax of PF-06380101 Unconjugated Payload
Query!
Assessment method [21]
0
0
Cmax is maximum observed serum concentration. Cmax for PF-06380101 unconjugated payload was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Small molecule components (PF-06380101) of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK.
Query!
Timepoint [21]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [22]
0
0
Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload
Query!
Assessment method [22]
0
0
Tmax is the time for Cmax. Tmax for PF-06380101 unconjugated payload was observed directly from data as time of first occurrence.Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [22]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [23]
0
0
t1/2 of PF-06380101 Unconjugated Payload
Query!
Assessment method [23]
0
0
Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [23]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Query!
Secondary outcome [24]
0
0
AUCinf of PF-06380101 Unconjugated Payload
Query!
Assessment method [24]
0
0
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [24]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
Query!
Secondary outcome [25]
0
0
AUCtau of PF-06380101 Unconjugated Payload
Query!
Assessment method [25]
0
0
Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [25]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Query!
Secondary outcome [26]
0
0
Rac of PF-06380101 Unconjugated Payload
Query!
Assessment method [26]
0
0
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Query!
Timepoint [26]
0
0
Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Query!
Eligibility
Key inclusion criteria
* HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only)
* HER2 positive and negative breast cancer (Part 2A)
* HER2 negative breast cancer (Part 1B & Part 2B)
* Performance status of 0 or 1
* Adequate bone marrow, kidney and liver function
Query!
Minimum age
18
Years
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Query!
Maximum age
No limit
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Query!
Sex
Both males and females
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Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Known CNS disease including, but not limited to, metastases
* History of exposure to certain cumulative doses of anthracyclines
* Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy
* Active and clinically significant bacterial, fungal, or viral infection
* Abnormal cardiac function defined by a LVEF <50% by ECHO or MUGA
* Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Query!
Query!
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Intervention assignment
Other
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Other design features
Query!
Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/11/2017
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
31/08/2021
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Sample size
Target
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Accrual to date
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Final
95
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Chris O'Brien Lifehouse - Camperdown
Query!
Recruitment hospital [2]
0
0
Macquarie University - Macquarie Park
Query!
Recruitment postcode(s) [1]
0
0
2050 - Camperdown
Query!
Recruitment postcode(s) [2]
0
0
2109 - Macquarie Park
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Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arizona
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Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
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Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Georgia
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Nebraska
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Texas
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Utah
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Country [7]
0
0
Italy
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State/province [7]
0
0
Lombardia
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Country [8]
0
0
Italy
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State/province [8]
0
0
MB
Query!
Country [9]
0
0
Italy
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State/province [9]
0
0
MI
Query!
Country [10]
0
0
Korea, Republic of
Query!
State/province [10]
0
0
Gyeonggi-do
Query!
Country [11]
0
0
Korea, Republic of
Query!
State/province [11]
0
0
Incheon
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Country [12]
0
0
Korea, Republic of
Query!
State/province [12]
0
0
Seoul
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Country [13]
0
0
Russian Federation
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State/province [13]
0
0
Stavropol Region
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Country [14]
0
0
Russian Federation
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State/province [14]
0
0
Saint-Petersburg
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Country [15]
0
0
Spain
Query!
State/province [15]
0
0
Madrid
Query!
Country [16]
0
0
Spain
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State/province [16]
0
0
Barcelona
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Pfizer
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.
Query!
Trial website
https://clinicaltrials.gov/study/NCT03284723
Query!
Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
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Address
0
0
Pfizer
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Country
0
0
Query!
Phone
0
0
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Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/23/NCT03284723/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/23/NCT03284723/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03284723
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