GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors

Genentech

Status and phase: Completed; Phase 1

Conditions: Solid Cancers

Treatments: Drug: capecitabine; Drug: bevacizumab; Drug: GDC-0980; Drug: mFOLFOX6

Study type: Interventional

Funder types: Industry

Identifiers

NCT01332604

PIM4945g

GO00883 (Other Identifier)

Details and patient eligibility

About

This is an open-label, multicenter, Phase Ib, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-0980 administered in combination with capecitabine and with mFOLFOX6 chemotherapy with bevacizumab added on at Cycle 5 in patients with advanced or metastatic solid tumors.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically documented locally advanced or metastatic solid tumors for which established therapy is ineffective, not tolerable, or does not exist
• Patients with histologically or cytologically documented locally advanced or metastatic breast cancer who have received at least one prior chemotherapy-based regimen for incurable disease (Arm A)
• Patients with histologically or cytologically documented locally advanced or metastatic CRC who have not received prior oxaliplatin-based therapy within 1 year of initiation of study treatment. (Arm B)

Exclusion criteria

• Prior anti-cancer therapy that fulfills the following criteria: a total of more than six courses of an alkylating agent, a total of more than four courses of carboplatin-containing chemotherapy regimens, and a total of more than two courses of nitrosoureas or mitomycin C, high-dose chemotherapy requiring stem-cell support, and irradiation to >= 25% of bone marrow-bearing areas
• Current dyspnea at rest because of complications of advanced malignancy or other disease requiring continuous oxygen therapy
• Known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Bisphosphonate therapy for symptomatic hypercalcemia
• Known untreated or active central nervous system (CNS) metastases
• Pregnancy, lactation, or breastfeeding

For Arm B:

• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• History of myocardial infarction or unstable angina within 6 months prior to the first dose of study treatment
• History of stroke or transient ischemic attacks within 6 months prior to the first dose of study treatment
• Significant vascular disease within 6 months prior to the first dose of study treatment
• History of hemoptysis within 1 month prior to the first dose of study treatment
• Patients with one or more pulmonary tumor masses with evidence of cavitation
• Evidence of bleeding diathesis or significant coagulopathy
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of study treatment
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to the first dose of study treatment
• Clinical signs or symptoms of GI obstruction or requirement for parenteral hydration, parenteral nutrition, or tube feeding
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• The presence of an ulcerating breast cancer tumor will not render a patient ineligible
• Proteinuria

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 2 patient groups

A

Experimental group

Treatment:

Drug: GDC-0980

Drug: capecitabine

B

Experimental group

Treatment:

Drug: GDC-0980

Drug: bevacizumab

Drug: mFOLFOX6