Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    GDC-0077
Previous Study | Return to List | Next Study

To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03006172
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE December 22, 2016
First Posted Date  ICMJE December 30, 2016
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE December 13, 2016
Estimated Primary Completion Date December 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Stage 1: Percentage of Participants With Dose Limiting Toxicities [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  • Recommended Phase II Dose of GDC-0077 [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  • Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Day 1 up to 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
  • Stage 1: Percentage of Participants With Dose Limiting Toxicities [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  • Recommended Phase II Dose of GDC-0077 [ Time Frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35) ]
  • Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Day 1 up to 3.5 years ]
Change History Complete list of historical versions of study NCT03006172 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to end of study (EOS; up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • AUC from Time Zero to Dosing Interval (AUC0-tau) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Half-Life of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Maximum Plasma Concentration (Cmax) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Minimum Plasma Concentration (Cmin) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Time to Cmax (tmax) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Apparent Clearance (CL/F) of GDC-0077 [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • Accumulation Ratio (AR) of GDC-0077 at Steady-State [ Time Frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days) ]
  • AUC of Palbociclib [ Time Frame: Predose (0-2 hours before GDC-0077) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days ]
  • Cmax of Palbociclib [ Time Frame: Predose (0-2 hours before GDC-0077) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days ]
  • AUC of Letrozole [ Time Frame: Predose (0-2 hours before GDC-0077 dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days ]
  • Cmax of Letrozole [ Time Frame: Predose (0-2 hours before GDC-0077 dosing) on Cycle 1 Day 1 up to EOS (up to approximately 5 years); Cycle length=28 days ]
  • AUC of Fulvestrant [ Time Frame: Cycle 1 Day 2 up to EOS (up to approximately 5 years); Cycle length=28 days. ]
  • Cmax of Fulvestrant [ Time Frame: Cycle 1 Day 2 up to EOS (up to approximately 5 years); Cycle length=28 days. ]
  • Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1) [ Time Frame: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 5 years) ]
  • Duration of Response, as Assessed by RECIST v1.1 [ Time Frame: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
  • Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
  • Progression Free Survival (PFS) as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 5 years) ]
  • Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of GDC-0077 Treatment [ Time Frame: Baseline, Week 2 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
  • Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cycle (Cy) 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to end of study (EOS). Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • AUC from Time Zero to Dosing Interval (AUC0-tau) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cycle (Cy) 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to end of study (EOS). Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Half-Life of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Maximum Plasma Concentration (Cmax) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Minimum Plasma Concentration (Cmin) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Time to Cmax (tmax) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Apparent Clearance (CL/F) of GDC-0077 [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • Accumulation Ratio (AR) of GDC-0077 at Steady-State [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stage 1 Arm A: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy 1 Days 1, 15; Cy1 Days 2, 3, 16; predose, 2 hr postdose on Cy1 Day 8; predose on Cy 1 Days 22, 29, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm B: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stage II, Arm D: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 8, 15; Cy1 Days 2, 3, 9, 10, 16; 2h postdose on Cy1 Day 10; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before dosing; EOS=up to approximately 3.5 years; Cycle length=28 days (Cy1 of Stage 1 Arm A=35 days).
  • AUC of Palbociclib [ Time Frame: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days ]
  • Cmax of Palbociclib [ Time Frame: Predose, 0.5, 1, 2, 3, 4, 8 hr postdose on Cy1 Days 1, 15; Cy1 Days 2, 16; predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days ]
  • AUC of Letrozole [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stages I and II, Arm B: 1 hr post GDC-0077 dose on Cy1 Days 1;predose on Cy 1 Day 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing. EOS=up to approximately 3.5 years; Cycle length=28 days
  • Cmax of Letrozole [ Time Frame: Cycle 1 Day 1 up to study completion/early termination (up to approximately 3.5 years) (detailed timeframe is provided in outcome measure description section) ]
    Detailed timeframe: Stages I and II, Arm B: 1 hr post GDC-0077 dose on Cy1 Days 1;predose on Cy 1 Day 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Stages I and II, Arm C: Predose, 0.5, 3, 6 hr postdose on Cy1 Day 1; predose, 0.5, 1, 2, 4, 8 hr postdose on Cy2 Day 1; Day 2 of Cy1, 2; predose on Cy 1 Days 8, 15, Cy3-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing. EOS=up to approximately 3.5 years; Cycle length=28 days
  • AUC of Fulvestrant [ Time Frame: Cy1 Day 2, predose on Days 8, 15, 22; Predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days. ]
  • Cmax of Fulvestrant [ Time Frame: Cy1 Day 2, predose on Days 8, 15, 22; Predose on Cy 1 Days 22, Cy2-6 Day 1, Day 1 of each cycle thereafter up to EOS. Predose=0-2 hr before GDC-0077 dosing; EOS=up to approximately 3.5 years; Cycle length=28 days. ]
  • Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1) [ Time Frame: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 3.5 years) ]
  • Duration of Response, as Assessed by RECIST v1.1 [ Time Frame: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  • Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  • Progression Free Survival (PFS) as Assessed by RECIST v1.1 [ Time Frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years) ]
  • Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of GDC-0077 Treatment [ Time Frame: Baseline, Week 2 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE To Evaluate the Safety, Tolerability, and Pharmacokinetics of GDC-0077 Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer
Official Title  ICMJE A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted Therapies in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Hormone-Receptor Positive Breast Cancer
Brief Summary This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of GDC-0077 administered orally as a single agent in participants with locally advanced or metastatic Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA)-mutant solid tumors, including breast cancer, and in combination with standard-of-care endocrine and targeted therapies for the treatment of locally advanced or metastatic PIK3CA-mutant hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Participants will be enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II). Participants will be assigned to one of six regimens: GDC-0077 as a single agent (Arm A), GDC-0077 in combination with palbociclib and letrozole (Arm B), GDC-0077 in combination with letrozole (Arm C), GDC-0077 in combination with fulvestrant (Arm D), GDC-0077 in combination with palbociclib and fulvestrant (Arm E), and GDC-0077 in combination with palbociclib, fulvestrant, and metformin (Arm F).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Solid Tumor
Intervention  ICMJE
  • Drug: GDC-0077
    Participants will receive oral GDC-0077 once daily on Days 1-28 of each cycle.
    Other Name: RO7113755
  • Drug: Fulvestrant
    Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.
  • Drug: Letrozole
    Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
  • Drug: Palbociclib
    Participants will receive once daily oral doses of palbociclib 125 mg on Days 1−21 of each cycle.
  • Drug: Metformin
    Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
Study Arms  ICMJE
  • Experimental: Stage I Arm A: GDC-0077 Single Agent
    Participants will receive GDC-0077 in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of GDC-0077 on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Intervention: Drug: GDC-0077
  • Experimental: Stage I Arm B: GDC-0077 + Palbociclib + Letrozole
    Participants will receive GDC-0077 in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1−21, and letrozole on Days 1−28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Letrozole
    • Drug: Palbociclib
  • Experimental: Stage I Arm C: GDC-0077 + Letrozole
    Participants will receive GDC-0077 in escalating dose levels along with letrozole on Days 1−28 of each 28-day cycle. The starting dose of GDC-0077 will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Letrozole
  • Experimental: Stage II Arm B: GDC-0077 + Palbociclib + Letrozole
    Participants will receive GDC-0077 on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of GDC-0077 will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Letrozole
    • Drug: Palbociclib
  • Experimental: Stage II Arm C: GDC-0077 + Letrozole
    Participants will receive GDC-0077 in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of GDC-0077 will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Letrozole
  • Experimental: Stage II Arm D: GDC-0077 + Fulvestrant
    Participants will receive GDC-0077 on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of GDC-0077 will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Fulvestrant
  • Experimental: Stage II Arm E: GDC-0077 + Palbociclib + Fulvestrant
    Participants will receive GDC-0077 (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of GDC-0077 will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Fulvestrant
    • Drug: Palbociclib
  • Experimental: Stage II Arm F: GDC-0077+Palbociclib+Fulvestrant+Metformin
    Participants will receive GDC-0077 (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of GDC-0077 will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
    Interventions:
    • Drug: GDC-0077
    • Drug: Fulvestrant
    • Drug: Palbociclib
    • Drug: Metformin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
236
Original Estimated Enrollment  ICMJE
 (submitted: December 27, 2016)
156
Estimated Study Completion Date  ICMJE December 14, 2021
Estimated Primary Completion Date December 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evaluable or measurable disease per RECIST, Version 1.1 (measurable disease only for Arm D)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of greater than or equal to (≥) 12 weeks
  • Adequate hematologic and organ function, including blood counts, liver and kidney function

Stage I Arm A (GDC-0077):

- Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer

Stages I and II, Arms B and C:

- Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer

Stage II, Arms D, E, or F:

- Female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer

Stage II Arms D:

- Prior treatment with CDK4/6 inhibitor

Stages I and II:

- All participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation by central laboratory test.

Exclusion Criteria:

  • Inflammatory or metaplastic breast cancer
  • History of leptomeningeal disease
  • Type 1 or 2 diabetes requiring anti-hyperglycemic medication
  • Inability or unwillingness to swallow pills
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • Known and untreated, or active central nervous system metastases
  • Uncontrolled pleural effusion or ascites
  • History of other malignancy within 5 years, except for treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
  • History of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease
  • Congenital long QT syndrome, prolonged QT interval, or family history of sudden unexplained death or long QT syndrome

Stage II:

  • Stage II Arms B, C, D, and E only: Prior treatment with >1 chemotherapy regimen for metastatic disease
  • Prior treatment with PI3K inhibitor
  • History of significant toxicity related to mTOR inhibitor requiring treatment discontinuation
  • Stage II Arms B and E only: prior CDK4/6 inhibitor treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: GO39374 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Canada,   France,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03006172
Other Study ID Numbers  ICMJE GO39374
2016-003022-17 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP