A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer

NCT ID: NCT00960960

Last Updated: 2016-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2015-12-31

Brief Summary

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage.

Conditions

Breast Cancer

Keywords

MBC; PI3K; Avastin; Herceptin

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab

Pictilisib 60 mg will be administered orally (PO) once daily (QD) for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 milligrams per meter square (mg/m\^2) intravenously (IV) on Days 1, 8, and 15 and bevacizumab 10 milligrams per kilogram (mg/kg) IV on Days 1 and 15 of each 28-day cycle. In Cohort 1 (Part 1), pictilisib will be evaluated with paclitaxel only; participants in Cohort 1 (Part 1) will be eligible to receive bevacizumab starting at Cycle 2. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab

Pictilisib 100 mg will be administered PO QD for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part 2 (Arm A: Cohort 1a): Pictilisib 165 mg + Paclitaxel

Pictilisib 165 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part 2 (Arm A: Cohort 2a): Pictilisib 250 mg + Paclitaxel

Pictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part 2 (Arm A: Cohort 3a): Pictilisib 330 mg + Paclitaxel

Pictilisib 330 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab

Pictilisib 200 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab

Pictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab

Pictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab

Pictilisib 180 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.

Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab

Pictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m\^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.

Part 3: Pictilisib 260 mg + Letrozole

Pictilisib 260 mg will be administered PO QD continuously with letrozole 2.5 mg PO QD for each 28-day cycle. Study treatment will continue until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Pictilisib

Intervention Type: DRUG

Pictilisib will be administered PO QD on escalating doses.

Letrozole

Intervention Type: DRUG

Letrozole will be administered PO at a dose of 2.5 mg QD for for each 28-day cycle.

Interventions

Bevacizumab

Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.

Intervention Type: DRUG

Pictilisib

Pictilisib will be administered PO QD on escalating doses.

Intervention Type: DRUG

Letrozole

Letrozole will be administered PO at a dose of 2.5 mg QD for for each 28-day cycle.

Intervention Type: DRUG

Paclitaxel

Paclitaxel will be administered IV at a dose of 90 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.

Intervention Type: DRUG

Trastuzumab

Trastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

Avastin; GDC-0941; Herceptin

Eligibility Criteria

Inclusion Criteria

• Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
• Adequate organ and bone marrow function as assessed by laboratory tests
• Evaluable disease or disease measurable per RECIST
• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria

• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
• Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment
• Uncontrolled current illness
• Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)
• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• Known HIV infection
• New York Heart Association (NYHA) Class II or greater congestive heart failure
• Active ventricular arrhythmia requiring medication
• Pregnancy, lactation, or breastfeeding
• Known significant hypersensitivity to study drugs or excipients
• History of arterial thromboembolic disease within 6 months of first study treatment
• No more than two prior chemotherapy regimens for metastatic disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stina Singel, M.D., Ph.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Peoria, Illinois, United States

Boston, Massachusetts, United States

Nashville, Tennessee, United States

Leuven, , Belgium

Milan, Lombardy, Italy

Countries

United States; Belgium; Italy

References

Schoffski P, Cresta S, Mayer IA, Wildiers H, Damian S, Gendreau S, Rooney I, Morrissey KM, Spoerke JM, Ng VW, Singel SM, Winer E. A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer. Breast Cancer Res. 2018 Sep 5;20(1):109. doi: 10.1186/s13058-018-1015-x.

Reference Type: DERIVED

PMID: 30185228 (View on PubMed)

Other Identifiers

GO01304

Identifier Type: OTHER

Identifier Source: secondary_id

2009-010781-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GDC4629g

Identifier Type: -

Identifier Source: org_study_id