Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Progression Free Survival (PFS) |
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016) |
|
| Primary |
PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors |
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors |
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Overall Survival (OS) |
OS was defined as the time from the date of randomization to the date of death from any cause. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019) |
|
| Secondary |
OS in Participants With PTEN-Low Tumors |
OS was defined as the time from the date of randomization to the date of death from any cause. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019) |
|
| Secondary |
OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
OS was defined as the time from the date of randomization to the date of death from any cause. |
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019) |
|
| Secondary |
Objective Response Rate (ORR) |
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
ORR in Participants With PTEN-Low Tumors |
Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
Confirmed tumor ORR in subjects with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of subjects who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Subjects for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Duration of Response |
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Duration of Response in Participants With PTEN-Low Tumors |
Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
Duration of objective response in participants with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Time to Disease Progression |
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Time to Disease Progression in Participants With PTEN-Low Tumors |
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
Time to disease progression was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1. |
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016) |
|
| Secondary |
Safety: Percentage of Participants With Adverse Events |
An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months) |
|
| Secondary |
Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib |
PK parameters were not calculated due to sparse PK sampling. |
Cycle 1 Day 1, Cycle 1 Day 8 |
|
| Secondary |
Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib |
PK parameters were not calculated due to sparse PK sampling. |
Cycle 1 Day 1, Cycle 1 Day 8 |
|
| Secondary |
Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score |
EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1=Not at all to 4=Very much; 2 questions used 7-point scale [1=very poor to 7=Excellent]). Scores averaged, transformed to 0-100 scale; a higher score=better level of functioning. For symptom scale scores, higher level=severe level of symptoms. "A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). PRO measures were analyzed from baseline up to cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5). |
Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1 |
|
| Secondary |
PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30 |
Subjects reporting >/= 10-point increase compared to baseline (Cycle 1 Day 1) were considered "improved", those reporting <10-point difference were considered "remained stable", and those reporting >/=10-point decrease were considered "worsened". A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). Patient reported outcome measures were analyzed from baseline up to and including cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5). |
Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1 |
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