Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer
Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer
This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells
PRIMARY OBJECTIVES:
I. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).
SECONDARY OBJECTIVES:
I. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility
OUTLINE: This is a multicenter study.
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies.
After completion of study treatment, patients are followed periodically for up to 2 years.
Inclusion Criteria:
Diagnosis of stage IV colorectal cancer (histologic proof is not required)
Measurable disease
Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy
Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available
Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor
No known brain metastasis
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Life expectancy ≥ 6 months
Hemoglobin ≥ 9.0 g/dL
Absolute neutrophil count (ANC) ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
White blood cell count (WBC) ≥ 3,400/mm³
International normalized ratio (INR) < 1.5 (≤ 3.0 if on anti-coagulation therapy [e.g., warfarin or heparin])
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if there is liver involvement)
Alkaline phosphatase ≤ 3 times ULN
Creatinine ≤ 1.5 times ULN
Urine protein:creatinine ratio < 1 OR urine dipstick < 2+ OR urine protein < 1,000 mg by 24-hour urine collection
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment (≥ 2 weeks after completion of treatment with sorafenib tosylate alone)
Willing to provide mandatory blood samples for translational research studies
Able to swallow whole pills
No inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg on anti-hypertensive medications)
No prior hypertensive crisis or hypertensive encephalopathy
No myocardial infarction or unstable angina within the past 6 months
No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
No hemorrhage or bleeding event > grade 3 within the past 4 weeks
No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
No greater than normal risk of bleeding
No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
No concurrent uncontrolled illness including, but not limited to, any of the following:
No known HIV infection or chronic hepatitis B or C infection
No serious, non-healing wound, active ulcer, or untreated bone fracture
No significant traumatic injury within the past 4 weeks
No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study
No malabsorption problem
None of the following within the past 6 months:
No other active malignancy within the past 3 years except non melanoma skin cancer or carcinoma in situ of the cervix
No other concurrent investigational agent for this cancer
Prior radiotherapy allowed
No prior sorafenib tosylate
No prior discontinuation of bevacizumab due to adverse events
More than 4 weeks since prior and no concurrent participation in any other experimental drug study
More than 4 weeks since prior St. John's wort or rifampin
More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
More than 7 days since prior core biopsy or minor surgical procedure, including placement of a vascular access device
No concurrent anticoagulant, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis
Ann Arbor, Michigan 48106, United States
Eau Claire, Wisconsin 54703, United States