Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Paclitaxel With or Without Bevacizumab in Patients With Locally Recurrent or Metastatic Breast Cancer

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with taxane-based chemotherapy regimens utilized in patients with locally recurrent or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: bevacizumab; Drug: GDC-0980; Drug: paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Locally recurrent or metastatic breast cancer, not amenable to resection with curative intent
• For Arm C: Overexpression of HER2
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate hematologic and organ function
• Evaluable or measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors)
• Female patients of childbearing potential must use an acceptable method of contraception to prevent pregnancy and to continue its use for the duration of the study

Exclusion Criteria:

• Prior anti-cancer therapy of more than two regimens of systemic cytotoxic chemotherapy for advanced or metastatic breast cancer
• Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment
• History of Type 1 or Type 2 diabetes requiring regular medication
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Any condition requiring full-dose anticoagulants
• Leptomeningeal disease as a manifestation of cancer
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs, inhaled steroids, or the equivalent of <= 10 mg/day of prednisone
• Known clinically significant history of liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Known HIV infection
• Known untreated or active CNS metastases
• Pregnancy, lactation, or breastfeeding
• Major surgical procedure, open biopsy, or significant traumatic injury within a within a specified timeframe of the first dose of study treatment

For Arm B:

• Uncontrolled hypertension, complication from hypertension, myocardial infarctions, unstable angina, vascular disease or stroke within a specified timeframe of the first dose of study treatment
• Evidence of bleeding diathesis or significant coagulopathy including hemoptysis within a specified timeframe of the first dose of study treatment
• History of abdominal conditions (e.g., fistula, perforation, obstruction) that would preclude use of bevacizumab
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0980; Oral repeating dose; Drug: paclitaxel; Intravenous repeating dose
Experimental: B	Drug: bevacizumab; Intravenous repeating dose; Drug: GDC-0980; Oral repeating dose; Drug: paclitaxel; Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of dose-limiting toxicities (DLTs)	Through Day 22
Incidence, nature, and severity of adverse events	Through study completion, up to 1 year, or early discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters of GDC-0980, paclitaxel and bevacizumab (including total exposure, maximum and minimum plasma concentration, time to maximum observed plasma concentration, plasma half-life)	Through Day 22
Duration of response	Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation
Progression-free survival (PFS)	Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation
Objective tumor response	Assessed at periodic intervals until study completion, up to 1 year, or early discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Jennifer Lauchle, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: PIM4880g; GO00882 (Other Identifier: Hoffmann-La Roche)