Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Participants Resistant to Aromatase Inhibitor Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01437566
First received: September 8, 2011
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
This is a multicenter, international, randomized, double-blinded, placebo-controlled, Phase II trial. Participants with advanced breast cancer (ABC) or Metastatic Breast Cancer (MBC) who have experienced recurrence or progression of their disease while receiving aromatase inhibitor (AI) therapy or who have relapsed within 6 months after completing adjuvant AI therapy will be enrolled in Part I of this study. Participants with ABC or MBC who have received prior AI therapy and who have PIK3CA-mutant tumors will be enrolled in Part II of this study. Part I of the study will assess the effect of the addition of GDC-0941 to fulvestrant (Arm A) and of GDC-0980 to fulvestrant (Arm B) on progression free survival (PFS) compared with fulvestrant + placebo (Arm C). Part II of the study will examine the safety and tolerability and to estimate the effect of GDC-0941 in combination with fulvestrant (Arm D) on PFS versus fulvestrant + placebo (Arm E) in participants who received prior treatment with an AI and whose tumors contain a PIK3CA mutation.

Condition Intervention Phase
Breast Cancer
Drug: Fulvestrant
Drug: GDC-0941
Drug: GDC-0941 Matching Placebo
Drug: GDC-0980
Drug: GDC-0980 Matching Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Placebo Controlled, Randomized Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Patients Resistant to Aromatase Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Progression Free Survival as Assessed by the Investigator Per modified RECIST v 1.1 [ Time Frame: From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline to up to 30 days after the last dose of study drug (Approximately 5 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Objective Tumor Response (Complete Response [CR] or Partial Response [PR] as Assessed by the Investigator Per Modified RECIST v 1.1 [ Time Frame: From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Clinical Benefit Response Defined as PR, CR, or SD Per Modified RECIST v 1.1 [ Time Frame: From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy) ] [ Designated as safety issue: No ]
  • Duration of Confirmed Objective Response as Assessed by the investigator Per Modified RECIST v 1.1 [ Time Frame: From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy) ] [ Designated as safety issue: No ]
  • Percentage of Participants with PIK3CA Mutant Tumors [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Time to Maximum Plasma Concentration (Tmax) of GDC-0941 and GDC-0948 [ Time Frame: Part 1:0-4 hour (hr) predose (PrD), 1,2,4 hr postdose (PoD) on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration (Cmax) of GDC-0941 and GDC-0948 [ Time Frame: Part 1:0-4 hr PrD, 1,2,4 hr PoD on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Area Under the Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of GDC-0941 and GDC-0948 [ Time Frame: Part 1:0-4 hr PrD, 1,2,4 hr PoD on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1 ] [ Designated as safety issue: No ]

Enrollment: 318
Study Start Date: October 2011
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: GDC-0941 Matching Placebo + Fulvestrant (Arm E)
Participants with PIK3CA mutation will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 matching placebo QD orally starting on Day 1 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0941 Matching Placebo
Participants will receive GDC-0941 matching placebo QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Experimental: GDC-0941-260 mg + Fulvestrant (Arm D)
Participants with PIK3CA mutation will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 260 mg QD orally starting on Day 1 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0941
Participants will receive GDC-0941 260 mg (Part II) or 340 mg (Part I) QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Experimental: GDC-0941-340 mg + Fulvestrant (Arm A)
Participants will receive fulvestrant 500 milligrams (mg) as 2 intramuscular (IM) injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 340 mg once daily (QD) orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0941
Participants will receive GDC-0941 260 mg (Part II) or 340 mg (Part I) QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Placebo Comparator: GDC-0948 or GDC-0980 Matching Placebo + Fulvestrant (Arm C)
Participants will be randomized in 1:1 ratio to receive GDC-0948 matching placebo or GDC-0980 matching placebo with fulvestrant. Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0948 or GDC-0980 matching placebo QD orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0941 Matching Placebo
Participants will receive GDC-0941 matching placebo QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0980 Matching Placebo
Participants will receive GDC-0980 matching placebo QD orally from Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Experimental: GDC-0980-30 mg + Fulvestrant (Arm B)
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0980 30 mg QD orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Drug: GDC-0980
Participants will receive GDC-0980 30 mg (Part I) QD orally from Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

  Eligibility

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • As per national or local treatment guidelines, endocrine therapy (i.e., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not necessary for participants, at time of entry into the study.
  • Part I: Postmenopausal women with locally ABC or MBC whose disease relapsed during treatment with (or within 6 months after discontinuation of) an AI in the adjuvant setting or progressed during treatment with an AI in the metastatic setting.
  • Part II: Postmenopausal women with locally ABC or MBC whose disease has progressed during or after treatment with an AI. Participants who discontinued the AI for toxicity rather than completion of regimen or for disease progression are not eligible
  • Estrogen receptor (ER)-positive disease and human epidermal receptor 2 (HER2)-negative disease
  • Participants must have measurable disease by response evaluation criteria in solid tumors (RECIST) version (v) 1.1 or bone-only disease with radiologic scans
  • Adequate hematologic and end-organ function

Exclusion Criteria:

  • Prior treatment with fulvestrant, phosphoinositide 3-kinase (PI3K) inhibitor, or mechanistic target of rapamycin (mTOR) inhibitor for ABC or MBC
  • Prior anti-cancer therapy or radiotherapy within 2 weeks prior to Day 1 of Cycle 1
  • Prior treatment with greater than (>) one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on > two endocrine therapies for MBC
  • Participants requiring anti-hyperglycemic therapy
  • Clinically significant cardiac or pulmonary dysfunction
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption
  • Clinically significant history of liver disease
  • Active uncontrolled autoimmune disease or active inflammatory disease
  • Immunocompromised status
  • Need for current chronic corticosteroid therapy
  • Pregnancy, lactation, or breastfeeding
  • Current severe, uncontrolled systemic disease
  • Symptomatic hypercalcemia
  • Known untreated or active central nervous system (CNS) metastases
  • History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or patients who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence
  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: NCT01437566

  Show 130 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Gallia Levy, M.D., Ph.D. Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01437566     History of Changes
Other Study ID Numbers: GDC4950g  GO00769  2010-023763-17 
Study First Received: September 8, 2011
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 21, 2016