Clinical Trials /

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

NCT03006172

Description:

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).

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: GO39374
  • SECONDARY ID: 2016-003022-17
  • NCT ID: NCT03006172

Conditions

  • Breast Cancer
  • Solid Tumor

Interventions

DrugSynonymsArms
GDC-0077RO7113755Stage I Arm A: GDC-0077 Single Agent
FulvestrantStage II Arm D: GDC-0077 + Fulvestrant
LetrozoleStage I Arm B: GDC-0077 + Palbociclib + Letrozole
PalbociclibStage I Arm B: GDC-0077 + Palbociclib + Letrozole

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).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Stage I Arm A: GDC-0077 Single AgentExperimentalParticipants 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.
  • GDC-0077
    Stage I Arm B: GDC-0077 + Palbociclib + LetrozoleExperimentalParticipants 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.
    • GDC-0077
      • Letrozole
      • Palbociclib
    Stage I Arm C: GDC-0077 + LetrozoleExperimentalParticipants 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.
    • GDC-0077
      • Letrozole
      Stage II Arm B: GDC-0077 + Palbociclib + LetrozoleExperimentalParticipants 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.
      • GDC-0077
        • Letrozole
        • Palbociclib
      Stage II Arm C: GDC-0077 + LetrozoleExperimentalParticipants 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.
      • GDC-0077
        • Letrozole
        Stage II Arm D: GDC-0077 + FulvestrantExperimentalParticipants 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.
        • GDC-0077
        • Fulvestrant

          Eligibility 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

          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:All
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure: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)
          Safety Issue:
          Description:

          Secondary Outcome Measures

          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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)
          Safety Issue:
          Description: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).
          Measure: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
          Safety Issue:
          Description:
          Measure: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
          Safety Issue:
          Description:
          Measure: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)
          Safety Issue:
          Description: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
          Measure: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)
          Safety Issue:
          Description: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
          Measure: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.
          Safety Issue:
          Description:
          Measure: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.
          Safety Issue:
          Description:
          Measure: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)
          Safety Issue:
          Description:
          Measure: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)
          Safety Issue:
          Description:
          Measure: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)
          Safety Issue:
          Description:
          Measure: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)
          Safety Issue:
          Description:
          Measure: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
          Safety Issue:
          Description:

          Details

          Phase:Phase 1
          Primary Purpose:Interventional
          Overall Status:Recruiting
          Lead Sponsor:Genentech, Inc.

          Trial Keywords

            Last Updated

            January 6, 2017