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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001072-11 | EudraCT Number |
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The decision to not open the Phase III portion was based on a strategic sponsor decision and not driven by any safety concerns.
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The open-label Phase Ib portion of this study will 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 randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b and Phase 3: Ipatasertib + Palbociclib +Fulvestrant | Experimental |
| |
| Phase 3: Placebo + Palbociclib + Fulvestrant | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ipatasertib | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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). | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Piedmont Cancer Institute, PC | Atlanta | Georgia | 30318 | United States | ||
| University of Chicago Medical Center |
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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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.
Participants were enrolled in this study at 12 investigative centers in 7 countries from 21 November 2019 to 29 August 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase Ib: Ipatasertib + Palbociclib +Fulvestrant | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 12, 2020 |
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|
|
| Placebo | Drug | 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. |
|
| Palbociclib | Drug | Palbociclib, administered PO QD on Days 1-21 of each 28-day cycle. |
|
| Fulvestrant | Drug | 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. |
|
| Up to 36 Months |
| Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720 | Plasma concentrations of Ipatasertib and its metabolite G-037720 are reported. | 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) |
| Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma | Cmax of ipatasertib and its metabolite G-037720 in plasma is reported. | Cycle 1: Day 1 and Day 15 |
| Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720 | AUC0-24 of Ipatasertib and its metabolite G-037720 is reported | Cycle 1: Day 1 and Day 15 |
| Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720 | Tmax of ipatasertib and its metabolite G-037720 isreported. | Cycle 1: Day 1 and Day 15 |
| Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1 | 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. | From randomization in Phase III up to approximately 36 months |
| Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1 | 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. | 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 |
| Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1 | 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. | 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 |
| Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1 | OS was defined as the time from randomization to death from any cause. | 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 |
| Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF) | 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. | From randomization in Phase III to the first documentation of a ≥2-point increase in pain scale (up to approximately 36 months) |
| 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 | 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. | From randomization in Phase III to the first documentation of a ≥10-point increase (up to approximately 36 months) |
| Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), GHS/QoL According to EORTC QLQ-C30 | 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). | 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) |
| Phase III: Number of Participants With Adverse Events | 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. | Up to approximately 36 months |
| Chicago |
| Illinois |
| 60637 |
| United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114-2621 | United States |
| Dana-Farber Cancer Institute; GYN Oncology | Boston | Massachusetts | 02215 | United States |
| Summit Medical Group; MD Anderson Cancer Center | Florham Park | New Jersey | 07932 | United States |
| Cabrini Medical Centre; Oncology | Malvern | Victoria | 3144 | Australia |
| Sunshine Hospital | St Albans | Victoria | 3021 | Australia |
| Hospital das Clinicas - UFRGS | Porto Alegre | Rio Grande do Sul | 90035-903 | Brazil |
| Hospital Sao Lucas - PUCRS | Porto Alegre | Rio Grande do Sul | 90610-000 | Brazil |
| Tom Baker Cancer Centre-Calgary | Calgary | Alberta | T2N 4N2 | Canada |
| Juravinski Cancer Clinic; Clinical Trials Department | Hamilton | Ontario | L8V 5C2 | Canada |
| Hopital du Saint Sacrement | Québec | Quebec | G1S 4L8 | Canada |
| National Hospital Organization Kyushu Cancer Center | Fukuoka | 811-1395 | Japan |
| Kanagawa Cancer Center | Kanagawa | 241-8515 | Japan |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Vall d?Hebron Institute of Oncology (VHIO), Barcelona | Barcelona | 08035 | Spain |
| Hospital Clínico Universitario de Valencia; Servicio de Oncología | Valencia | 46010 | Spain |
| The Royal Marsden Hospital; Dept of Medicine | London | SW3 5PT | United Kingdom |
| Christie Hospital NHS Trust | Manchester | M20 4BX | United Kingdom |
| Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit | Sutton | SM2 5PT | United Kingdom |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Intent to Treat (ITT) population included all the enrolled participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase Ib: Ipatasertib + Palbociclib +Fulvestrant | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 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 initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | 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 | 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) | 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. | Safety evaluable population included all randomized participants who received any amount of study drug (i.e., ipatasertib + palbociclib + fulvestrant). | Posted | Count of Participants | Participants | Up to 36 Months |
| |||||||||||||||||||||
| Secondary | Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 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 | Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma | Cmax of ipatasertib and its metabolite G-037720 in plasma is reported. | PK-evaluable population included all participants who received study treatment. Overall number analyzed is the number of participants with data available for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1: Day 1 and Day 15 |
|
| |||||||||||||||||||
| Secondary | Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720 | AUC0-24 of Ipatasertib and its metabolite G-037720 is reported | PK-evaluable population included all participants who received study treatment. Overall number analyzed is the number of participants with data available for analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanograms/milliliter (h*ng/mL) | Cycle 1: Day 1 and Day 15 |
|
| |||||||||||||||||||
| Secondary | Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720 | Tmax of ipatasertib and its metabolite G-037720 isreported. | PK-evaluable population included all participants who received study treatment. Overall number analyzed is the number of participants with data available for analysis. | Posted | Median | Full Range | hours | Cycle 1: Day 1 and Day 15 |
|
| |||||||||||||||||||
| Secondary | Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1 | 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 initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | From randomization in Phase III up to approximately 36 months |
| |||||||||||||||||||||||
| Secondary | Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1 | 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. | The study was terminated before initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | 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 | Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1 | 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. | The study was terminated before initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | 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 | Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1 | OS was defined as the time from randomization to death from any cause. | The study was terminated before initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | 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 | Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF) | 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 initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | From randomization in Phase III to the first documentation of a ≥2-point increase in pain scale (up to approximately 36 months) |
| |||||||||||||||||||||||
| Secondary | 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 | 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. | The study was terminated before initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | From randomization in Phase III to the first documentation of a ≥10-point increase (up to approximately 36 months) |
| |||||||||||||||||||||||
| Secondary | Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), GHS/QoL According to EORTC QLQ-C30 | 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). | The study was terminated before initiation of Phase III as per sponsor's decision; hence this outcome measure was not assessed or analyzed, and no data collected. | Posted | 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 | Phase III: Number of Participants With Adverse Events | 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. | No data was collected because the study was terminated before the initiation of Phase III per the sponsor's decision. | Posted | Up to approximately 36 months |
|
Up to 36 months
Safety evaluable population included all randomized participants who received any amount of study drug (i.e., ipatasertib + palbociclib + fulvestrant).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase Ib: Ipatasertib + Palbociclib +Fulvestrant | 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. | 0 | 20 | 4 | 20 | 20 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Pseudomembranous colitis | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dacryostenosis acquired | Eye disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Application site pain | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Chills | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Pain | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Injection site infection | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Varicella zoster virus infection | Infections and infestations | MedDRA version 26.0. | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Animal bite | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Muscle injury | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Radiation pneumonitis | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA version 26.0. | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 26.0. | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Sacral pain | Musculoskeletal and connective tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Paresis | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Cellulite | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 26.0. | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA version 26.0. | Systematic Assessment |
|
The study was terminated before initiation of Phase III as per sponsor's decision; hence no primary efficacy and secondary efficacy, safety and pharmacokinetic outcome measures were assessed or analyzed, and no data was collected for Phase III.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| Aug 23, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C583616 | ipatasertib |
| C500026 | palbociclib |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|
|
| OG001 | Phase III: Placebo + Palbociclib + Fulvestrant | Placebo PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day cycle 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. |
|
| OG001 |
| Phase III: Placebo + Palbociclib + Fulvestrant |
Placebo PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day cycle 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. |
|
| Participants |
|
|
| OG001 | Phase III: Placebo + Palbociclib + Fulvestrant | Placebo PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day cycle 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. |
|
| OG001 | Phase III: Placebo + Palbociclib + Fulvestrant | Placebo PO QD along with palbociclib, 125 mg PO QD on Days 1-21 of each 28-day cycle 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. |
|
|