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: August 1, 2016
Last verified: August 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

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35294
United States, California
Hayward, California, United States, 94545
Oakland, California, United States, 94611
Roseville, California, United States, 95661
Sacramento, California, United States, 95825
San Francisco, California, United States, 94115
San Jose, California, United States, 95119
Santa Clara, California, United States, 95051
South San Francisco, California, United States, 94080
Vallejo, California, United States, 94589
Walnut Creek, California, United States, 94596
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Florida
Boca Raton, Florida, United States, 33428
Fort Myers, Florida, United States, 33916
Jacksonville, Florida, United States, 32224
Saint Petersburg, Florida, United States, 33705
United States, Georgia
Marietta, Georgia, United States, 30060
United States, Illinois
Joliet, Illinois, United States, 60435
Peoria, Illinois, United States, 61615
United States, Kansas
Wichita, Kansas, United States, 67214-3728
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02215
United States, Missouri
St. Louis, Missouri, United States, 63128
United States, New Jersey
Basking Ridge, New Jersey, United States, 07920
Hackensack, New Jersey, United States, 07601
United States, New York
Commack, New York, United States, 11725
New York, New York, United States, 10065
Rockville Centre, New York, United States, 11570
Sleepy Hollow, New York, United States, 10591
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
Germantown, Tennessee, United States, 38138
Nashville, Tennessee, United States, 37211
Nashville, Tennessee, United States, 37232
United States, Texas
Dallas, Texas, United States, 75246
Fort Worth, Texas, United States, 76104
Houston, Texas, United States, 77030-4095
Houston, Texas, United States, 77030
Tyler, Texas, United States, 75702
United States, Virginia
Richmond, Virginia, United States, 23226
Argentina
Buenos Aires, Argentina, 1025
Santa Fe, Argentina, 03000
Australia, New South Wales
Kogarah, New South Wales, Australia, 2217
Wahroonga, New South Wales, Australia, 2076
Australia, Queensland
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Bedford Park, South Australia, Australia, 5042
Woodville, South Australia, Australia, 5011
Australia, Victoria
Frankston, Victoria, Australia, 3199
Parkville, Victoria, Australia, 3050
Belgium
Bruxelles, Belgium, 1000
Bruxelles, Belgium, 1070
Edegem, Belgium, 2650
Leuven, Belgium, 3000
Liège, Belgium, 4000
Canada, Quebec
Montreal, Quebec, Canada, H3G 1A4
Quebec City, Quebec, Canada, G1R 2J6
Canada, Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Chile
Santiago, Chile, 7630370
Temuco, Chile, 4810469
Valparaiso, Chile, 2341391
Vina del Mar, Chile, 2540364
Czech Republic
Brno, Czech Republic, 656 53
Olomouc, Czech Republic, 775 20
Praha 2, Czech Republic, 128 08
Denmark
Herlev, Denmark, 2730
København Ø, Denmark, 2100
Odense, Denmark, 5000
Roskilde, Denmark, 4000
Vejle, Denmark, 7100
Århus, Denmark, 8000
France
Paris, France, 75231
Germany
Berlin, Germany, 13125
Düsseldorf, Germany, 40225
Freiburg, Germany, 79106
Freiburg, Germany, 79110
Hamburg, Germany, 20246
Muenchen, Germany, 81377
Muenchen, Germany, 81675
München, Germany, 80336
Trier, Germany, 54290
Hong Kong
Hong Kong, Hong Kong, 852
Pokfulam, Hong Kong
Israel
Beer Sheva, Israel, 8410101
Holon, Israel, 58100
Jerusalem, Israel, 91120
Jerusalem, Israel, 9372212
Kfar-Saba, Israel, 4428164
Rehovot, Israel, 7610001
Tel Aviv, Israel, 6423906
Tel-Hashomer, Israel, 52621
Zerifin, Israel, 70300
Italy
Napoli, Campania, Italy, 80131
Meldola, Emilia-Romagna, Italy, 47014
Milano, Lombardia, Italy, 20121
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20141
Monza, Lombardia, Italy, 20900
Pisa, Toscana, Italy, 56100
Prato, Toscana, Italy, 59100
Terni, Umbria, Italy, 05100
Korea, Republic of
Seoul, Korea, Republic of, 138-736
Malaysia
Kuala Lumpur, Malaysia, 56000
Kuala Lumpur, Malaysia, 59100
Penang, Malaysia, 10050
Penang, Malaysia, 10400
Tanjung Bungah, Malaysia, 11200
Mexico
León, Mexico, 37000
New Zealand
Christchurch, New Zealand
Hamilton, New Zealand, 3240
Wellington, New Zealand, 0621
Peru
Lima, Peru, 11
Lima, Peru, 34
Lima, Peru, Lima 27
Russian Federation
Chelyabinsk, Russian Federation, 454087
Kazan, Russian Federation, 420029
Moscow, Russian Federation, 115478
Voronezh, Russian Federation, 394000
Singapore
Singapore, Singapore, 119074
Spain
Barcelona, Spain, 08035
Lerida, Spain, 25198
Valencia, Spain, 46015
Zaragoza, Spain, 50009
Thailand
Patumwan, Thailand, 10330
Songkhla, Thailand, 90110
United Kingdom
Brighton, United Kingdom, BN1 9PX
Cardiff, United Kingdom, CF14 2TL
London, United Kingdom, SW3 6JJ
London, United Kingdom, W1G 6AD
Stoke on Trent, United Kingdom, ST4 7LN
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: August 1, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 24, 2016