Clinical trial NCT01437566: Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Participants Resistant to Aromatase Inhibitor Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-09-21
Enrollment: 318
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Progression Free Survival as Assessed by the Investigator Per modified RECIST v 1.1
timeFrame: 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)
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline to up to 30 days after the last dose of study drug (Approximately 5 years)
Secondary outcomes:
measure: 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
timeFrame: 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)
measure: Percentage of Participants with Clinical Benefit Response Defined as PR, CR, or SD Per Modified RECIST v 1.1
timeFrame: 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)
measure: Duration of Confirmed Objective Response as Assessed by the investigator Per Modified RECIST v 1.1
timeFrame: 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)
measure: Percentage of Participants with PIK3CA Mutant Tumors
timeFrame: Baseline
measure: Time to Maximum Plasma Concentration (Tmax) of GDC-0941 and GDC-0948
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of GDC-0941 and GDC-0948
timeFrame: 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
measure: Area Under the Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of GDC-0941 and GDC-0948
timeFrame: 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
Other outcomes:
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city: Rockville Centre
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city: Woodville
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city: Bruxelles
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city: Edegem
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city: Leuven
country: Belgium
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country: Belgium
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
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city: Saskatoon
country: Canada
state: Saskatchewan
city: Santiago
country: Chile
city: Temuco
country: Chile
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country: Chile
city: Vina del Mar
country: Chile
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country: Czech Republic
city: Olomouc
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Herlev
country: Denmark
city: København Ø
country: Denmark
city: Odense
country: Denmark
city: Roskilde
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country: Denmark
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city: Berlin
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city: Hamburg
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city: Pokfulam
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city: Holon
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city: Rehovot
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city: Tel Aviv
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city: Tel-Hashomer
country: Israel
city: Zerifin
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city: Napoli
country: Italy
state: Campania
city: Meldola
country: Italy
state: Emilia-Romagna
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Monza
country: Italy
state: Lombardia
city: Pisa
country: Italy
state: Toscana
city: Prato
country: Italy
state: Toscana
city: Terni
country: Italy
state: Umbria
city: Seoul
country: Korea, Republic of
city: Kuala Lumpur
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Penang
country: Malaysia
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country: Malaysia
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country: Malaysia
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country: New Zealand
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city: Lima
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city: Lima
country: Peru
city: Chelyabinsk
country: Russian Federation
city: Kazan
country: Russian Federation
city: Moscow
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city: Voronezh
country: Russian Federation
city: Singapore
country: Singapore
city: Barcelona
country: Spain
city: Lerida
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Patumwan
country: Thailand
city: Songkhla
country: Thailand
city: Brighton
country: United Kingdom
city: Cardiff
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Stoke on Trent
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Gallia Levy, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.