Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
Condition: Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: sorafenib tosylate; bevacizumab
Intervention description: Given orally; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Sorafenib; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of stage IV colorectal cancer (histologic proof is not required)

          -  Measurable disease

               -  Spiral CT scan required for both pre- and post-treatment tumor assessments of
                  lesions measuring 1-2 cm

          -  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

               -  Patients with neurological symptoms must undergo a CT scan or MRI of the brain to
                  exclude 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:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia requiring anti-arrhythmic drugs

               -  Psychiatric illness or social situations that would limit compliance with study
                  requirements

          -  No known HIV infection or chronic hepatitis B or C infection

          -  No serious, non-healing wound, active ulcer, or untreated bone fracture

               -  Patients with fractures secondary to metastatic disease are eligible after
                  appropriate radiotherapy

          -  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:

               -  Significant vascular disease (e.g., aortic aneurysm or aortic dissection)

               -  Peripheral arterial thrombosis

               -  Symptomatic peripheral vascular disease

               -  Abdominal fistula

               -  Gastrointestinal perforation

               -  Intra-abdominal abscess

          -  No other active malignancy within the past 3 years except non melanoma skin cancer or
             carcinoma in situ of the cervix

               -  Prior malignancy allowed provided patient is not receiving other specific
                  treatment for that malignancy (other than hormonal therapy)

          -  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