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

NCT ID: NCT01437566

Last Updated: 2016-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2016-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Fulvestrant

Intervention Type DRUG

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.

GDC-0941 Matching Placebo

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

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.

GDC-0941

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

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.

GDC-0941

Intervention Type DRUG

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.

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.

Group Type PLACEBO_COMPARATOR

Fulvestrant

Intervention Type DRUG

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.

GDC-0941 Matching Placebo

Intervention Type DRUG

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.

GDC-0980 Matching Placebo

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

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.

GDC-0980

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gallia Levy, M.D., Ph.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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Birmingham, Alabama, United States

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Hayward, California, United States

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Oakland, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Santa Clara, California, United States

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South San Francisco, California, United States

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Vallejo, California, United States

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Walnut Creek, California, United States

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Washington D.C., District of Columbia, United States

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Boca Raton, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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St. Petersburg, Florida, United States

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Marietta, Georgia, United States

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Joliet, Illinois, United States

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Peoria, Illinois, United States

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Wichita, Kansas, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Basking Ridge, New Jersey, United States

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Hackensack, New Jersey, United States

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Commack, New York, United States

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New York, New York, United States

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Rockville Centre, New York, United States

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Sleepy Hollow, New York, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Chattanooga, Tennessee, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Tyler, Texas, United States

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Richmond, Virginia, United States

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Buenos Aires, , Argentina

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Santa Fe, , Argentina

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Kogarah, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Bedford Park, South Australia, Australia

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Woodville, South Australia, Australia

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Frankston, Victoria, Australia

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Parkville, Victoria, Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Santiago, , Chile

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Temuco, , Chile

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Valparaíso, , Chile

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Viña del Mar, , Chile

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Brno, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Aarhus, , Denmark

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Herlev, , Denmark

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København Ø, , Denmark

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Odense, , Denmark

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Roskilde, , Denmark

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Vejle, , Denmark

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Paris, , France

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Berlin, , Germany

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Düsseldorf, , Germany

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Freiburg im Breisgau, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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München, , Germany

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München, , Germany

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München, , Germany

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Trier, , Germany

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Hong Kong, , Hong Kong

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Pokfulam, , Hong Kong

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Beersheba, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Tel Litwinsky, , Israel

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Ẕerifin, , Israel

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Napoli, Campania, Italy

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Meldola, Emilia-Romagna, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Monza, Lombardy, Italy

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Pisa, Tuscany, Italy

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Prato, Tuscany, Italy

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Terni, Umbria, Italy

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George Town, , Malaysia

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George Town, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Tanjung Bungah, , Malaysia

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León, , Mexico

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Christchurch, , New Zealand

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Hamilton, , New Zealand

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Wellington, , New Zealand

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Chelyabinsk, , Russia

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Kazan', , Russia

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Moscow, , Russia

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Voronezh, , Russia

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Singapore, , Singapore

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Seoul, , South Korea

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Barcelona, Barcelona, Spain

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Lleida, Lerida, Spain

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Valencia, Valencia, Spain

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Zaragoza, Zaragoza, Spain

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Patumwan, , Thailand

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Songkhla, , Thailand

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Brighton, , United Kingdom

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Cardiff, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Stoke-on-Trent, , United Kingdom

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Countries

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Brazil Hungary United States Argentina Australia Belgium Canada Chile Czechia Denmark France Germany Hong Kong Israel Italy Malaysia Mexico New Zealand Peru Russia Singapore South Korea Spain Thailand United Kingdom

References

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Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):811-821. doi: 10.1016/S1470-2045(16)00106-6. Epub 2016 May 4.

Reference Type DERIVED
PMID: 27155741 (View on PubMed)

Other Identifiers

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GO00769

Identifier Type: OTHER

Identifier Source: secondary_id

2010-023763-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GDC4950g

Identifier Type: -

Identifier Source: org_study_id