Clinical Trial Results:
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
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Summary
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EudraCT number |
2019-001072-11 |
Trial protocol |
ES |
Global end of trial date |
29 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Sep 2024
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First version publication date |
12 Sep 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CO41012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04060862 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, Hoffmann-La Roche, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Aug 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Aug 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of the Phase Ib portion of the trial was to evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The Phase III portion of this trial was never initiated.
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Nov 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 3
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Country: Number of subjects enrolled |
Japan: 2
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Country: Number of subjects enrolled |
Brazil: 5
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
United States: 2
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Country: Number of subjects enrolled |
Korea, Democratic People's Republic of: 1
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Worldwide total number of subjects |
20
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EEA total number of subjects |
6
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled in this study at 12 investigative centers in 7 countries from 15 November 2019 to 29 August 2023. | ||||||||||||||||
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Pre-assignment
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Screening details |
This study was planned to include two phases- Phase Ib and Phase III. No participant was enrolled in Phase III as the study was terminated early. | ||||||||||||||||
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Period 1
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Period 1 title |
Phase Ib (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Phase Ib: Ipatasertib + Palbociclib +Fulvestrant | ||||||||||||||||
Arm description |
Participants received ipatasertib 300 mg orally (PO) once daily (QD) during an initial 5-7 day during run-in and thereafter on Days 1-21 of each cycle (Cycle length= 28 days) along with palbociclib, 125 mg PO QD on Days 1-21 of each cycle and fulvestrant, 500 mg, intramuscularly (IM) on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent cycle for a maximum of 35 months. Only the first 10 participants received single agent ipatasertib during the initial 5-7 day safety run-in. After safety assessment of the run-in participants, further participants were enrolled in this arm to start receiving study treatments on Cycle 1 Day 1. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Ipatasertib
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Investigational medicinal product code |
RO5532961, GDC-0068
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ipatasertib 300 mg, PO QD during an initial 5-7 day run-in period, then continued on Days 1-21 of Cycle 1 and each subsequent cycle (Cycle length= 28 days) thereafter.
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Investigational medicinal product name |
Fulvestrant
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle.
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Investigational medicinal product name |
Palbociclib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Palbociclib 125 mg, PO QD on Days 1-21 of each 28-day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Phase Ib: Ipatasertib + Palbociclib +Fulvestrant
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Reporting group description |
Participants received ipatasertib 300 mg orally (PO) once daily (QD) during an initial 5-7 day during run-in and thereafter on Days 1-21 of each cycle (Cycle length= 28 days) along with palbociclib, 125 mg PO QD on Days 1-21 of each cycle and fulvestrant, 500 mg, intramuscularly (IM) on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent cycle for a maximum of 35 months. Only the first 10 participants received single agent ipatasertib during the initial 5-7 day safety run-in. After safety assessment of the run-in participants, further participants were enrolled in this arm to start receiving study treatments on Cycle 1 Day 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Phase Ib: Ipatasertib + Palbociclib +Fulvestrant
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Reporting group description |
Participants received ipatasertib 300 mg orally (PO) once daily (QD) during an initial 5-7 day during run-in and thereafter on Days 1-21 of each cycle (Cycle length= 28 days) along with palbociclib, 125 mg PO QD on Days 1-21 of each cycle and fulvestrant, 500 mg, intramuscularly (IM) on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent cycle for a maximum of 35 months. Only the first 10 participants received single agent ipatasertib during the initial 5-7 day safety run-in. After safety assessment of the run-in participants, further participants were enrolled in this arm to start receiving study treatments on Cycle 1 Day 1. | ||
Subject analysis set title |
Phase III: Ipatasertib + Palbociclib +Fulvestrant
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Ipatasertib, 300 mg PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day cycle and fulvestrant, 500 mg, IM injections on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent 28-day cycle until progressive disease (PD) or unacceptable toxicity, whichever occurs first.
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Subject analysis set title |
Phase III: Placebo + Palbociclib + Fulvestrant
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Placebo PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day and fulvestrant, 500 mg IM injection on Days 1 and 15 of Cycle 1, then on Day 1 of each subsequent 28-day cycle until PD or unacceptable toxicity, whichever occurs first.
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End point title |
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) [1] | ||||||||||||
End point description |
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). The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Primary
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End point timeframe |
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
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses is not relevant for this endpoint. |
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| Notes [2] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [3] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
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) | ||||||||||||||||
End point description |
An AE is 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. Safety evaluable population included all randomized participants who received any amount of study drug (i.e., ipatasertib + palbociclib + fulvestrant).
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End point type |
Secondary
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End point timeframe |
Up to 36 Months
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Phase Ib: Plasma Concentration of Ipatasertib and its Metabolite G-037720 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Plasma concentrations of Ipatasertib and its metabolite G-037720 are reported. Pharmacokinetic (PK)-evaluable population included all participants who received study treatment. Number analyzed is the number of participants with data available for analysis.
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End point type |
Secondary
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End point timeframe |
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)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and its Metabolite G-037720 in Plasma | ||||||||||||||||
End point description |
Cmax of ipatasertib and its metabolite G-037720 in plasma are reported. PK-evaluable population included all participants who received study treatment. Number analyzed is the number of participants with data available for analysis.
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End point type |
Secondary
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End point timeframe |
Cycle 1: Day 1 and Day 15
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and its Metabolite G-037720 | ||||||||||||||||
End point description |
Tmax of ipatasertib and its metabolite G-037720 are reported. PK-evaluable population included all participants who received study treatment. Number analyzed is the number of participants with data available for analysis.
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End point type |
Secondary
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End point timeframe |
Cycle 1: Day 1 and Day 15
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and its Metabolite G-037720 | ||||||||||||||||
End point description |
AUC0-24 of Ipatasertib and its metabolite G-037720 is reported. PK-evaluable population included all participants who received study treatment. Number analyzed is the number of participants with data available for analysis.
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End point type |
Secondary
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End point timeframe |
Cycle 1: Day 1 and Day 15
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1 | ||||||||||||
End point description |
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. The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
From randomization in Phase III up to approximately 36 months
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| Notes [4] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [5] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1 | ||||||||||||
End point description |
DOR=time from first occurrence of documented objective response to first occurrence of disease progression per the investigator per RECIST v1.1, or death from any cause, whichever occurs first. Objective response per RECIST v1.1 criteria: CR=disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR=at least 30% decrease in sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=at least 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to relative increase of 20%, SOD must also demonstrate absolute increase of ≥5 mm. Stable disease (SD)=neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. The study was terminated before initiation of Phase III, per sponsor’s decision. Hence, no participants were enrolled, & no data were collected or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
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
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| Notes [6] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [7] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1 | ||||||||||||
End point description |
CBR = percentage of participants with CR/PR, or SD for at least 24 weeks, as determined by investigator per RECIST v1.1. CR = disappearance of all target lesions. Any pathological lymph nodes must have a reduction in the short axis to <10 mm. PR = at least a 30% decrease in sum of diameters of all target lesions, taking as reference baseline sum of diameters, in absence of CR. SD = neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. PD = at least a 20% increase in 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%, sum of diameters must also demonstrate an absolute increase of ≥ 5 mm. The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
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
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| Notes [8] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [9] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1 | ||||||||||||
End point description |
OS was defined as the time from randomization to death from any cause. The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
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
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| Notes [10] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [11] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF) | ||||||||||||
End point description |
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. The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
From randomization in Phase III to the first documentation of a ≥2-point increase in pain scale, (up to approximately 36 months)
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| Notes [12] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [13] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
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 | ||||||||||||
End point description |
TTD in presence & interference of pain=time from randomization to first documentation of ≥10-point increase from baseline in EORTC QLQ-C30 pain scale (items 9 & 19). EORTC QLQ-C30=validated 30-item measure assessing 5 aspects of participant functioning (physical, emotional, role, cognitive &social), 8 symptom scales (fatigue, nausea &vomiting, pain, dyspnea, insomnia, appetite loss, constipation, & diarrhea), financial difficulties &global health status/QoL. Functioning &symptoms items, scored on 4-point scale (1=not at all to 4=very much). Pain scale, scored on 4-point scale (1=Not at All to 4=Very Much) including Item 9: have you had pain? & Item 19: did pain interfere with your daily activity? both range from 1=not at All to 4=very much. Sub-scores are linearly transformed to a range of 0-100. High scores=worse pain symptoms. Study was terminated before initiation of Phase III, per sponsor’s decision. Hence, no participants were enrolled & no data was collected for this endpoint.
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End point type |
Secondary
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End point timeframe |
From randomization in Phase III to the first documentation of a ≥10-point increase (up to approximately 36 months)
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| Notes [14] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [15] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), and GHS/QoL According to EORTC QLQ-C30 | ||||||||||||
End point description |
TTD in PF, RF & GHS/QoL = time to first documented ≥10-point decrease from baseline in following scales of EORTC QLQ-C30: PF, RF & GHS/QoL. EORTC QLQ-C30 is 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 recall period of previous week. The PF scale has 5 questions about participants' physical functioning. PF & RF scales are scored on 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). Scores are linearly transformed to score range of 0-100, higher score indicate higher response level. The study was terminated before initiation of Phase III as per sponsor’s decision; hence this outcome measure was not assessed & no data collected.
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End point type |
Secondary
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End point timeframe |
From randomization in Phase III to the first documentation of a ≥10-point decrease in the PF, RF and GHS/QoL function of EORTC QLQ-C30, (up to approximately 36 months)
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| Notes [16] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [17] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Phase III: Number of Participants with Adverse Events | |||||||||
End point description |
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. The study was terminated before the initiation of Phase III, as per the sponsor’s decision. Hence, no participants were enrolled, and no data were collected, assessed, or analyzed for this endpoint.
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End point type |
Secondary
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End point timeframe |
Up to approximately 36 months
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| Notes [18] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. [19] - No participants were enrolled in Phase III as the study was terminated early per sponsors decision. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Upto 36 months
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Adverse event reporting additional description |
Safety evaluable population included all randomized participants who received any amount of study drug (i.e., ipatasertib + palbociclib + fulvestrant).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Phase 1b: Ipatasertib + Palbociclib +Fulvestrant
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Reporting group description |
Participants received ipatasertib 300 mg PO QD during an initial 5-7 day run-in, and thereafter on Days 1-21 of each cycle (Cycle length= 28 days) along with palbociclib, 125 mg PO QD on Days 1-21 of each cycle and fulvestrant, 500 mg, IM on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent cycle for a maximum of 35 months. Only the first 10 participants received single agent ipatasertib during the initial 5-7 day safety run-in. After safety assessment of the run-in participants, further participants were enrolled in this arm to start receiving study treatments on Cycle 1 Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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14 Oct 2019 |
- Risks Associated with Palbociclib: The new risk, interstitial lung disease (ILD)/pneumonitis was added.
- Section on Pneumonitis was updated to reflect this new risk and to state the specific guidance required for palbociclib. Additional safety measures were added to the Adverse Event Management Guidance.
- Inclusion Criteria and Exclusion Criteria, the timing of the contraception requirement and the corresponding intent to become pregnant after permanent discontinuation of study treatment given the differential requirements for fulvestrant based on different local prescribing information was clarified. |
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12 Feb 2020 |
- Restriction of relapse specifically during the initial 5 years was removed throughout
the protocol.
- Pneumonitis was added to the list of potentially overlapping toxicities that may be exacerbated when combining ipatasertib and palbociclib.
- Addition of “worst pain” item from the Brief Pain Inventory-Short Form (BPI-SF) and European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Breast Cancer Module 23 (EORTC QLQ-BR23).
- Eligibility criteria for the phase III portion were updated to no longer allow prior CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer.
- The sampling window for post-dose PK samples for Phase III patients on Cycle 1,
Day 1 and Cycle 1, Day 15 were updated and aligned with that on Cycle 2, Day 15 so that PK can be compared between cycles more easily - A clarification was added that after the end of the adverse event reporting period, only participants in the Phase III portion of the study will be followed for long-term survival.
- An additional exclusion criterion of no more than 1 prior line of endocrine-based therapy for Phase III participants was added.
- Guidance for resuming palbociclib for Grade 1 interstitial lung disease/pneumonitis was provided.
- The screening windows for participants in Phase Ib were updated for consistency with
the remainder of the protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| Due to the early termination Phase III portion of the trial was not evaluated. | |||||||
