Clinical trial NCT01332604: GDC-0980 in Combination With a Fluoropyrimidine, Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 30 days after last dose of study treatment
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Up to Day 21 for Arm A and up to Day 28 for Arm B
measure: Nature of adverse events graded according to NCI CTCAE, v4.0
timeFrame: Up to 30 days after last dose of study treatment
measure: Nature of dose limiting toxicities (DLTs)graded according to NCI CTCAE, v4.0
timeFrame: Up to 28 days
measure: Severity of adverse events
timeFrame: Up to 30 days after last dose of study treatment
Secondary outcomes:
measure: Total exposure from Time 0 to the last measurable concentration
timeFrame: Up to Day 2 for Arm B and up to Day 9 for Arm A
measure: Maximum observed plasma concentration
timeFrame: Up to Day 2 for Arm B and up to Day 9 for Arm A
measure: Minimum observed plasma concentration
timeFrame: Up to Day 2 for Arm B and up to Day 9 for Arm A
measure: Time to maximum observed plasma concentration
timeFrame: Up to Day 2 for Arm B and up to Day 9 for Arm A
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Rochester
country: United States
state: Minnesota
city: Barcelona
country: Spain
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: