Solid Cancers
Conditions
Brief summary
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.
Interventions
DRUGGDC-0980
Oral escalating dose
DRUGbevacizumab
Intravenous repeating dose
DRUGcapecitabine
Oral repeating dose
DRUGmFOLFOX6
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Spain, United States
Outcome results
None listed