Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00960960
First received: August 13, 2009
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) GDC-0941 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 (GDC-0941 will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (GDC-0941 will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (GDC-0941 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.

Condition Intervention Phase
Metastatic Breast Cancer, Locally Advanced Breast Cancer
Drug: Bevacizumab
Drug: GDC-0941
Drug: Letrozole
Drug: Paclitaxel
Drug: Trastuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety And Pharmacology of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, And With Letrozole in Patients With Locally Recurrent Or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Incidence, and nature of dose-limiting toxicity [ Time Frame: 30 days after the last dose of study treatment (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Incidence, nature, and severity of adverse events [ Time Frame: 30 days after the last dose of study treatment (up to approximately 6.5 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Minimum serum concentrations [ Time Frame: 30 days after the last dose of study treatment (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Objetive response [ Time Frame: on Days 22-28 of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: on Days 22-28 of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: on Days 22-28 of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Area under curve from time zero to last measurable concentrations [ Time Frame: 30 days after the last dose of study treatment (up to approximately 6.5 years) ] [ Designated as safety issue: No ]
  • Maximum serum concentrations [ Time Frame: 30 days after the last dose of study treatment (up to approximately 6.5 years) ] [ Designated as safety issue: No ]

Enrollment: 71
Study Start Date: August 2009
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GDC-0941
Participants with locally recurrent or metastatic breast cancer will receive PO GDC-0941 administered with letrozole once daily (QD) of each 28-day cycle or 90 milligrams per meter square (mg/m^2) IV paclitaxel on Days 1, 8, and 15 with and without 10 milligrams per kilogram (mg/kg) IV bevacizumab on Days 1 and 15 of each 28-day cycle, or with 2-4 mg/kg IV trastuzumab on Days 1, 8, 15, and 22 of each 28-day cycle).
Drug: Bevacizumab
Bevacizumab will be administered IV at a dose of 10 mg/kg
Drug: GDC-0941
GDC-0491 will be administered PO at a dose of 260 mg.
Drug: Letrozole
Letrozole will be administered PO at a dose of 2.5 mg QD.
Drug: Paclitaxel
Paclitaxel will be administered IV at a dose of 90 mg/m^2.
Drug: Trastuzumab
Trastuzumab will be administered IV at a dose of 2-4 mg/kg.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 Response Evaluation Criteria in Solid Tumors (RECIST)
  • Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

  • History of Grade >= 3 fasting hyperglycemia
  • History of diabetes requiring regular medication
  • 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, or hormonal therapy) within a specified timeframe of the first dose of study treatment
  • Uncontrolled current illness
  • Active autoimmune disease requiring the equivalent of >10 mg/day of prednisone
  • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with 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
  • No prior taxane therapy for metastatic disease
  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: NCT00960960

Locations
United States, Illinois
Peoria, Illinois, United States, 61615
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Tennessee
Nashville, Tennessee, United States, 37232
Belgium
Leuven, Belgium, 3000
Italy
Milano, Lombardia, Italy, 20133
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Stina Singel, M.D., Ph.D. Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00960960     History of Changes
Other Study ID Numbers: GDC4629g  GO01304  2009-010781-38 
Study First Received: August 13, 2009
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
MBC
PI3K
Avastin
Herceptin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Letrozole
Albumin-Bound Paclitaxel
Bevacizumab
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 23, 2016