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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04060862




Registration number
NCT04060862
Ethics application status
Date submitted
13/08/2019
Date registered
19/08/2019

Titles & IDs
Public title
A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Scientific title
A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Secondary ID [1] 0 0
2019-001072-11
Secondary ID [2] 0 0
CO41012
Universal Trial Number (UTN)
Trial acronym
IPATunity150
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ipatasertib
Treatment: Drugs - Placebo
Treatment: Drugs - Palbociclib
Treatment: Drugs - Fulvestrant

Experimental: Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant -

Placebo comparator: Phase 3: Placebo + Palbociclib + Fulvestrant -


Treatment: Drugs: Ipatasertib
Phase 1b: Ipatasertib, 300 mg starting dose administered orally once daily (PO QD) during an initial 5-7 day run-in period, then continued on Days 1-21 during the first cycle. Starting with Cycle 2, Day 1 ipatasertib will be taken orally once daily on Days 1-21 of each 28-day cycle. Phase 3: Ipatasertib, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.

Treatment: Drugs: Placebo
Phase 3: Matching placebo, administered PO QD on Days 1-21 of each 28-day cycle at the dose confirmed in the Phase Ib portion.

Treatment: Drugs: Palbociclib
Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle.

Treatment: Drugs: Fulvestrant
Fulvestrant, 500 mg administered as two intramuscular injections of 250 mg each on Cycle 1 Days 1 and 15 and Day 1 of each subsequent 28-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase III: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Assessment method [1] 0 0
PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of = 5 millimeters (mm).
Timepoint [1] 0 0
From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
Secondary outcome [1] 0 0
Phase Ib: Number of Participants With Adverse Events and Adverse Events With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Assessment method [1] 0 0
AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. Severity of AEs were rated per NCI CTCAE v5 where, Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental Activities of Daily Living (ADL); Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 Life-threatening consequences; urgent intervention indicated; Grade 5 Death related to AE.
Timepoint [1] 0 0
Up to 36 Months
Secondary outcome [2] 0 0
Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720
Assessment method [2] 0 0
Plasma concentrations of Ipatasertib and its metabolite G-037720 are reported.
Timepoint [2] 0 0
Cycle 1, Day 1 and 15: 0.25 hours pre-dose, 0.5, 1, 2, 3, 4 and 6 hours post- dose ; Cycle 2, Day 15: 0.25 hours pre-dose; Cycle 3, Day 15: 0.15 hours pre-dose, 2 hours post-dose (each cycle = 28 days)
Secondary outcome [3] 0 0
Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma
Assessment method [3] 0 0
Cmax of ipatasertib and its metabolite G-037720 in plasma is reported.
Timepoint [3] 0 0
Cycle 1: Day 1 and Day 15
Secondary outcome [4] 0 0
Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720
Assessment method [4] 0 0
AUC0-24 of Ipatasertib and its metabolite G-037720 is reported
Timepoint [4] 0 0
Cycle 1: Day 1 and Day 15
Secondary outcome [5] 0 0
Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720
Assessment method [5] 0 0
Tmax of ipatasertib and its metabolite G-037720 isreported.
Timepoint [5] 0 0
Cycle 1: Day 1 and Day 15
Secondary outcome [6] 0 0
Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1
Assessment method [6] 0 0
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions =4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Timepoint [6] 0 0
From randomization in Phase III up to approximately 36 months
Secondary outcome [7] 0 0
Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1
Assessment method [7] 0 0
DOR was defined as time from first occurrence of a documented objective response to the first occurrence of disease progression as determined by investigator per RECIST v1.1, or death from any cause, whichever occurs first. Objective response was defined using RECIST v1.1 criteria as: CR = disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR = at least a 30% decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in absence of CR. PD = at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to relative increase of 20%, sum of diameters must also demonstrate an absolute increase of = 5 mm. Stable disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Timepoint [7] 0 0
From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
Secondary outcome [8] 0 0
Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1
Assessment method [8] 0 0
CBR was defined as the percentage of participants who had a CR or PR, or SD for at least 24 weeks, as determined by the investigator according to RECIST v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of = 5 mm.
Timepoint [8] 0 0
From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
Secondary outcome [9] 0 0
Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1
Assessment method [9] 0 0
OS was defined as the time from randomization to death from any cause.
Timepoint [9] 0 0
From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
Secondary outcome [10] 0 0
Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF)
Assessment method [10] 0 0
TTD in severity of pain is defined as the time from randomization to the first documentation of a 2-point or more increase from baseline on the "worst pain" item from the BPI-SF. A 2-point change is defined as clinically meaningful. The BPI-SF is a widely used patient-reported outcome (PRO) for assessing pain, and the "worst pain" item, frequently used for evaluating increases in the severity of pain. The BPI-SF asks participants to rate their pain at its worst in the last week on a scale from 0 (No pain) to 10 (pain as bad as one can imagine). Higher score indicates more pain.
Timepoint [10] 0 0
From randomization in Phase III to the first documentation of a =2-point increase in pain scale (up to approximately 36 months)
Secondary outcome [11] 0 0
Phase III: TTD in Presence and Interference of Pain According to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale
Assessment method [11] 0 0
TTD in presence \& interference of pain is defined as time from randomization to the first documentation of =10-point increase from baseline in EORTC QLQ-C30 pain scale (items 9 \& 19). EORTC QLQ-C30 is a validated 30-item self-report measure assessing 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), eight symptom scales (fatigue, nausea \& vomiting, pain, dyspnea, insomnia, appetite loss, constipation, \& diarrhea), financial difficulties, \& global health status/quality of life (GHS/QoL) with a recall period of the previous week. Functioning \& symptoms items are scored on a 4-point scale (1=Not at All to 4=Very Much). Pain scale is scored on a 4-point scale (1=Not at All to 4=Very Much) including Item 9: have you had pain? and Item 19: did pain interfere with your daily activity? both range from 1=Not at All to 4=Very Much. All sub-scores are linearly transformed to a total score range of 0-100. Higher scores indicate worse pain symptoms.
Timepoint [11] 0 0
From randomization in Phase III to the first documentation of a =10-point increase (up to approximately 36 months)
Secondary outcome [12] 0 0
Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), GHS/QoL According to EORTC QLQ-C30
Assessment method [12] 0 0
TTD in PF, RF and GHS/QoL is defined as the time to first documented =10-point decrease from baseline in following scales of the EORTC QLQ-C30: PF, RF and GHS/QoL. EORTC QLQ-C30 is a validated 30-item self-report measure assessing 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), eight symptom scales (fatigue, nausea \& vomiting, pain, dyspnea, insomnia, appetite loss, constipation, \& diarrhea), financial difficulties, \& GHS/QoL with a recall period of the previous week. The PF scale has 5 questions about participants' physical functioning and is scored on a 4-point scale (1=Not at All to 4=Very Much). The RF scale is scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL scale has 7 possible scores of responses (1=Very Poor to 7=Excellent). All sub-scores are linearly transformed to a total score range of 0-100. Higher scores indicate a higher response level (better functioning/QoL).
Timepoint [12] 0 0
From randomization in Phase III to the first documentation of a =10-point decrease in the PF, RF and GHS/QoL of EORTC QLQ-C30 (up to approximately 36 months)
Secondary outcome [13] 0 0
Phase III: Number of Participants With Adverse Events
Assessment method [13] 0 0
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition; any deterioration in a laboratory value or other clinical test; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Timepoint [13] 0 0
Up to approximately 36 months

Eligibility
Key inclusion criteria
* HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
* For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
* For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
* Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
* At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
* Phase III only: Tumor specimen from the most recently collected, available tumor tissue
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant
* Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
* Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
* Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
* Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
* History of Type I or Type II diabetes mellitus requiring insulin
* History of or active inflammatory bowel disease or active bowel inflammation
* Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/08/2023
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Cabrini Medical Centre; Oncology - Malvern
Recruitment hospital [2] 0 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
3144 - Malvern
Recruitment postcode(s) [2] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
Brazil
State/province [5] 0 0
RS
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Japan
State/province [9] 0 0
Fukuoka
Country [10] 0 0
Japan
State/province [10] 0 0
Kanagawa
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Valencia
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Manchester
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan
Statistical analysis plan Study Protocol and Statistical Analysis Plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04060862