Dose Dense Therapy and Bevacizumab in Solid Tumors and Colorectal Cancer

DISEASE CHARACTERISTICS:

• Phase I:

  • Histologically or cytologically confirmed solid tumor

    • Metastatic OR locally advanced unresectable disease
    • No curative therapy exists

  • Measurable or evaluable disease

    • Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques OR ≥ 10 mm with spiral CT scan
  • No known brain metastases

• Phase II:

  • Histologically or cytologically confirmed colorectal cancer

    • Metastatic OR locally advanced unresectable disease
  • Measurable disease (as defined in phase I)
  • No tumor involving major blood vessels
  • No evidence of CNS disease, including primary brain tumor or brain metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Life expectancy ≥ 12 weeks

• Absolute neutrophil count (ANC) ≥ 1,500/mm^3

  • ANC < 1,500/mm^3 allowed, if in the opinion of the investigator, this represents an ethnic or racial variation of normal
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 10.0 g/dL
• Bilirubin ≤ 1.5 mg/dL
• AST/ALT ≤ 2 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• Urine protein:creatinine ratio < 1.0 OR protein < 1 g by 24-hour urine collection (phase II)
• PT/INR ≤ 1.5 unless on full-dose anticoagulants (phase II)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use effective double-barrier contraception during and for 28 days (phase I) or 3 months (phase II) after completion of study treatment
• Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to capecitabine, irinotecan hydrochloride, oxaliplatin, or bevacizumab

• No other uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude study compliance
• No cardiac ischemia within the past 6 months (phase I)
• No New York Heart Association class II-IV congestive heart failure or symptomatic arrhythmia (phase II)

• No arterial thrombotic events within the past 6 months including, but not limited to, any of the following (phase II):

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina or angina requiring surgical or medical intervention
  • Myocardial infarction
• No clinically significant peripheral vascular disease (phase II)
• No history of hypertension unless well controlled (< 150/90 mm Hg) on an antihypertensive regimen (phase II)
• No evidence of bleeding diathesis or coagulopathy (phase II)
• No gastrointestinal (GI) perforation, abdominal fistula, or intra-abdominal abscess within the past 30 days (phase II)

• No significant history of bleeding events (phase II)

  • Patients with a history of significant bleeding episodes (e.g., hemoptysis or upper or lower GI bleeding) within the past 6 months are not eligible unless the source of bleeding has been resected
• No significant traumatic injury within the past 28 days (phase II)
• No serious or nonhealing wound, ulcer, or bone fracture (phase II)
• No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered (phase I)
• At least 2 weeks since prior immunotherapy or biologic therapy and recovered (phase I)
• No prior treatment for advanced or metastatic colorectal cancer (phase II)
• More than 12 months since prior adjuvant chemotherapy and/or biologic therapy (e.g., bevacizumab or cetuximab) and recovered (phase II)
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to the only site of measurable disease unless there is measurable disease progression within the radiation port after completion of radiotherapy
• No prior radiotherapy to ≥ 20% of the bone marrow
• More than 28 days since prior major surgical procedure* or open biopsy and recovered (phase II)
• More than 14 days since prior minor surgery* and recovered (phase II)

• Concurrent full-dose anticoagulation (e.g., warfarin) allowed provided the following criteria are met (phase II):

  • Patient has an in-range INR (between 2 and 3) and is on a stable dose of oral anticoagulants or a stable dose of low molecular weight heparin
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known varices)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent sargramostim (GM-CSF) NOTE: *Insertion of a vascular device is not considered major or minor surgery