A Study of the Safety and Pharmacology of GDC-0980 in Combination With Either Paclitaxel and Carboplatin (With or Without Bevacizumab) or Pemetrexed and Cisplatin in Patients With Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Either Paclitaxel and Carboplatin (With or Without Bevacizumab) or Pemetrexed and Cisplatin in Patients With Solid Tumors

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0980 administered with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin to patients with locally advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: bevacizumab; Drug: GDC-0980; Drug: paclitaxel; Drug: carboplatin; Drug: cisplatin; Drug: pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28050
• United States
  • California
    • Los Angeles, California, United States, 90025
  • Florida
    • Tampa, Florida, United States, 33612
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114

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:

• Histologically or cytologically documented, incurable, locally advanced, or metastatic solid malignancy
• Adequate hematologic and end organ function
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study
• Measurable disease per RECIST (Response Evaluable Criteria in Solid Tumors), with the exception of prostate cancer (two rising PSA Levels that meet the criteria of progression per PSA Working Group) and ovarian cancer (two rising CA-125 levels greater than the ULN)

Exclusion Criteria:

• Current dyspnea at rest due to complications of advanced malignancy, or other conditions requiring continuous supplemental oxygen
• Uncontrolled hypomagnesemia or hypokalemia
• History of Grade >= 3 fasting hyperglycemia
• Any condition requiring full-dose anticoagulants
• Known HIV infection
• Known untreated or active central nervous system (CNS) metastases
• Pregnancy, lactation, or breastfeeding
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study
• For Arm B: Conditions that preclude the use of bevacizumab
• For Arm C: Conditions that preclude the use of pemetrexed or cisplatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0980; Oral escalating dose; Drug: paclitaxel; Intravenous repeating dose; Drug: carboplatin; Intravenous repeating dose
Experimental: B	Drug: bevacizumab; Intravenous repeating dose; Drug: GDC-0980; Oral escalating dose; Drug: paclitaxel; Intravenous repeating dose; Drug: carboplatin; Intravenous repeating dose
Experimental: C	Drug: GDC-0980; Oral escalating dose; Drug: cisplatin; intravenous repeating dose; Drug: pemetrexed; intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Severity of adverse events	Up to 30 days after last dose of study treatment
Incidence of adverse events	Up to 30 days after last dose of study treatment or initiation of new anti-cancer therapy, whichever comes first
Incidence of dose limiting toxicities (DLTs)	Up to 21 days from Last Patient In (LPI) in Stage 1 of study
Nature of adverse events	Up to 30 days after last dose of study treatment or initiation of new anti-cancer therapy, whichever comes first
Nature of dose limiting toxicities (DLTs)	Up to 21 days from Last Patient In (LPI) in Stage 1 of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Total exposure	Up to 32 months or early study discontinuation
Maximum plasma concentration	Up to 32 months or early study discontinuation
Time to maximum observed plasma concentration	Up to 32 months or early study discontinuation
Plasma half-life	Up to 32 months or early study discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: February 18, 2011
• First Submitted That Met QC Criteria: February 21, 2011
• First Posted (Estimate): February 23, 2011

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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Bevacizumab; Pemetrexed
• Other Study ID Numbers: PIM4946g; GO01336 (Other Identifier: Hoffmann-La Roche)