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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib, Open Label, Dose Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: GDC-0980
* Drug: bevacizumab
* Drug: capecitabine
* Drug: mFOLFOX6


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: GDC-0980<br>* Oral escalating dose<br>Drug: capecitabine<br>* Oral repeating dose<br>|
| Experimental: B<br> | Drug: GDC-0980<br>* Oral escalating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: mFOLFOX6<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 30 days after last dose of study treatment | 
| Incidence of dose limiting toxicities (DLTs) |  | Up to Day 21 for Arm A and up to Day 28 for Arm B | 
| Nature of adverse events graded according to NCI CTCAE, v4.0 |  | Up to 30 days after last dose of study treatment | 
| Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0 |  | Up to 28 days | 
| Severity of adverse events |  | Up to 30 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total exposure from Time 0 to the last measurable concentration |  | Up to Day 2 for Arm B and up to Day 9 for Arm A | 
| Maximum observed plasma concentration |  | Up to Day 2 for Arm B and up to Day 9 for Arm A | 
| Minimum observed plasma concentration |  | Up to Day 2 for Arm B and up to Day 9 for Arm A | 
| Time to maximum observed plasma concentration |  | Up to Day 2 for Arm B and up to Day 9 for Arm A |