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Trial record 1 of 1 for:    GDC-0077
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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT03006172
First received: December 22, 2016
Last updated: January 6, 2017
Last verified: January 2017
  Purpose
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 four 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), or GDC-0077 in combination with fulvestrant (Arm D).

Condition Intervention Phase
Breast Cancer
Solid Tumor
Drug: GDC-0077
Drug: Fulvestrant
Drug: Letrozole
Drug: Palbociclib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 156
Study Start Date: November 2016
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
Other Name: RO7113755
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
Other Name: RO7113755
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. Dose modification will be done based on the safety and investigator's discretion.
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
Other Name: RO7113755
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. Dose modification will be done based on the safety and investigator's discretion.
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
Other Name: RO7113755
Drug: Letrozole
Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1−28 of each cycle.
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.
Drug: GDC-0077
Participants will receive oral GDC-0077 once daily. For dose escalation, the dose will be increased by up to 100% of the preceding dose level for each successive cohort, until a safety threshold is met. Once the safety threshold has been met in a given cohort, the dose will be increased by up to 50% of the preceding dose level for each successive cohort until a second cohort meets the safety threshold. Thereafter, the dose will be increased by up to 33% for each successive cohort.
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. Participants who received fulvestrant within 4 weeks of initiating study treatment will receive fulvestrant 500 mg on Day 1 of each Cycle starting in Cycle 1.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Evaluable or measurable disease per RECIST, Version 1.1
  • 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, Arm B:

  • Postmenopausal female participants with histologically documented locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer
  • Absolute neutrophil count ≥ 1500 per microliter

Stages I and II, Arm C or Stage II Arm D:

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

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. Confirmation of adequate tissue is required prior to enrollment. For participants enrolled to biopsy cohorts or who consent to optional tumor biopsies, the pretreatment tumor biopsy may be used

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
  • Serious infection requiring antibiotics
  • Concurrent ocular or intraocular condition that requires medical or surgical intervention to prevent or treat vision loss
  • Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis
  • Daily supplemental oxygen
  • History of or active inflammatory disease or active bowel inflammation
  • Symptomatic hypercalcemia requiring bisphosphonate or denosumab therapy
  • Significant traumatic injury or major surgical procedure within 4 weeks prior to starting study treatment
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Treatment with chemotherapy, immunotherapy, or biologic therapy as anti-cancer therapy within 3 weeks, or treatment with endocrine therapy or kinase inhibitors within 2 weeks, prior to starting study treatment, except for premenopausal participants with breast cancer who may continue Gonadotropin-releasing hormone agonist therapy
  • Radiation therapy as cancer therapy within 4 weeks, or palliative radiation to bony metastases within 2 weeks, prior to starting study treatment
  • 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
  • Current treatment with medications known to prolong the QT interval

Stage I:

  • History of significant toxicity related to another phosphatidylinositol 3-kinase (PI3K) inhibitor or mammalian target of rapamycin (mTOR) inhibitor requiring treatment discontinuation
  • Stage I Arm A: Pregnancy, lactation, or intention to become pregnant or fathering a child during the study
  • Stage I Arm B: history of significant toxicity related to cyclin-dependent kinase (CDK)4/6 inhibitor, bone marrow transplant or extensive radiotherapy to ≥25 percent (%) of bone marrow

Stage II:

  • 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 Arm B: prior CDK4/6 inhibitor treatment, bone marrow transplant or extensive radiotherapy to ≥25% of bone marrow
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03006172

Locations
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02114
Contact: Study Director       global.rochegenentechtrials@roche.com   
Recruiting
Boston, Massachusetts, United States, 02215
Contact: Study Director       global.rochegenentechtrials@roche.com   
United States, New York
Recruiting
New York, New York, United States, 10017
Contact: Study Director       global.rochegenentechtrials@roche.com   
Recruiting
New York, New York, United States, 10032
Contact: Study Director       global.rochegenentechtrials@roche.com   
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
Contact: Study Director       global.rochegenentechtrials@roche.com   
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03006172     History of Changes
Other Study ID Numbers: GO39374
2016-003022-17 ( EudraCT Number )
Study First Received: December 22, 2016
Last Updated: January 6, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Letrozole
Palbociclib
Estradiol
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 23, 2017