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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00437203




Registration number
NCT00437203
Ethics application status
Date submitted
16/02/2007
Date registered
19/02/2007
Date last updated
3/04/2012

Titles & IDs
Public title
PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine
Scientific title
Phase I Study of PF-00477736 With Gemcitabine In Patients With Advanced Solid Malignancies
Secondary ID [1] 0 0
A8211001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-00477736
Treatment: Drugs - gemcitabine

Experimental: 1 -


Treatment: Drugs: PF-00477736
Escalating doses of PF-00477736 will be administered intravenously on Days 2 and 9 and gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts).
If a patient is administered Cycle 0 - only PF-0047736 will be administered intravenously on Days 1 and 8 of a 21-day cycle for patients who have a 3-hour infusion and Days 1 and 8 of a 14-day cycle for patients who have a 24-hour infusion.

Treatment: Drugs: gemcitabine
gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine
Timepoint [1] 0 0
Up to Day 21 Cycle 1
Secondary outcome [1] 0 0
Number of Participants With Objective Response (OR) - OR based assessment of confirmed complete response(CR)/confirmed partial response(PR)/stable disease(SD)/progressive disease(PD) as per Response Evaluation Criteria in Solid Tumors(RECIST).CR:disappearance of target lesions;PR:at least(>=) 30% decrease in sum of longest dimensions of target lesions(reference:baseline sum of longest dimensions);PD:>=20% increase in sum of longest dimensions of target lesions(reference:smallest sum of longest dimensions recorded since treatment started)/appearance of any new lesions;SD:no adequate shrinkage to qualify for PR/adequate increase to qualify for PD.
Timepoint [1] 0 0
Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [2] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [3] 0 0
Minimum Observed Plasma Trough Concentration (Cmin)
Timepoint [3] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [4] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Timepoint [4] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [5] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Timepoint [5] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start: Day 1, 8 Cycle 0
Secondary outcome [6] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)] - AUC (0-48)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-48).
Timepoint [6] 0 0
0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [7] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Timepoint [7] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [8] 0 0
Concentration of PF-00477736 in Urine
Timepoint [8] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [9] 0 0
Plasma Decay Half-Life (t1/2) - Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Timepoint [9] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10
Secondary outcome [10] 0 0
Metabolite Profile of PF-00477736 in Plasma and Urine
Timepoint [10] 0 0
0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10

Eligibility
Key inclusion criteria
- Histological or cytopathological diagnosis of solid malignancy that is refractory to
standard therapy or for which no curative therapy exists.

- ECOG performance status 0 or 1.

- Adequate blood cell counts, kidney function and liver function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with gemcitabine.

- Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or
leptomeningeal disease.

- NCI CTC Grade 2 or higher ARDS, non-infectious pneumonitis, or pulmonary fibrosis.

- NCI CTC Grade 2 or higher cardiovascular toxicities with the exception of NCI CTC
Grade 3 hypertension that is well controlled.

- Known human immunodeficiency virus (HIV) seropositivity.

- Concurrent treatment with anticoagulants or known coagulopathy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To determine the overall safety of PF-00477736 when given in combination with gemcitabine, a
chemotherapy agent, in patients with advanced solid tumors and determine the maximum dose of
PF-00477736 that can be safely given in combination with gemcitabine. This is the first study
of PF-00477736 in humans.
Trial website
https://clinicaltrials.gov/show/NCT00437203
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00437203