OBJECTIVES:

Primary

• Determine the antitumor efficacy of SU011248 in patients with metastatic colorectal adenocarcinoma who failed prior treatment with irinotecan, oxaliplatin, and a fluoropyrimidine with or without bevacizumab.

Secondary

• Determine the onset and duration of tumor control and 1-year survival rate in patients treated with this drug.
• Determine the safety of this drug in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to prior bevacizumab (yes vs no).

Patients receive oral SU011248 once daily on days 1-28. Courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 76-126 patients (38-63 per stratum) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal adenocarcinoma not amenable to surgery, radiotherapy, or combined modality therapy with curative intent

• Must have received prior irinotecan, oxaliplatin, and a fluoropyrimidine in the adjuvant and/or advanced disease setting with or without bevacizumab (in the advanced disease setting) AND developed resistance to these prior therapies, as defined by one of the following:

  • Irinotecan-, oxaliplatin-, or fluoropyrimidine-resistant disease, defined as relapse or progression during treatment OR within 6 months after completing the most recent regimen
  • Bevacizumab-resistant disease, defined as disease progression during treatment OR within 6 months after completing bevacizumab

• At least one unidimensionally measurable lesion at least 20 mm by conventional radiographic techniques or MRI OR at least 10-16 mm by spiral CT scan

  • The following lesions are not considered measurable:

    • Bone lesions
    • Ascites
    • Peritoneal carcinomatosis or miliary lesions
    • Pleural or pericardial effusions
    • Lymphangitis of the skin or lung
    • Cystic lesions
    • Irradiated lesions
    • Disease documented by indirect evidence only (e.g., by laboratory test, such as alkaline phosphatase)
• No known brain or leptomeningeal disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if abnormalities are due to underlying malignancy)
• Albumin ≥ 3.0 g/dL
• Bilirubin ≤ 1.5 times ULN
• PT and PTT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• LVEF above lower limit of normal by MUGA
• No ongoing cardiac dysrhythmias ≥ grade 2
• No atrial fibrillation of any grade
• No prolongation of the QTc interval to > 450 msec (for males) or > 470 msec (for females)

• None of the following conditions within the past 12 months:

  • Myocardial infarction
  • Severe/unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident
  • Transient ischemic attack
  • Deep vein thrombosis
  • Other thromboembolic event

Pulmonary

• No pulmonary embolism within the past 12 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Amylase and lipase ≤ ULN
• Adrenocorticotrophic hormone stimulation test normal
• No known HIV infection
• No AIDS-related illness
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• At least 3 weeks since prior immunotherapy and recovered
• No prior vascular endothelial growth factor inhibitors (except bevacizumab)
• No concurrent biological response modifiers
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No more than 3 prior systemic chemotherapy-based regimens for advanced disease
• Prior chemoembolization therapy allowed provided areas of measurable disease are not affected
• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics

• At least 3 weeks since prior radiotherapy and recovered

  • Areas of measurable disease must not be affected

• No concurrent radiotherapy to the sole site(s) of measurable disease

  • Concurrent palliative radiotherapy allowed provided the measurable lesions (study target lesions) are not included in the irradiated field

Surgery

• Recovered from prior surgery
• Prior surgery allowed provided areas of measurable disease are not affected
• More than 12 months since prior coronary/peripheral artery bypass graft
• No concurrent surgery in the sole site(s) of measurable disease

Other

• Prior intrahepatic therapy or cryotherapy allowed provided areas of measurable disease are not affected
• No prior tyrosine kinase inhibitors (except bevacizumab)
• No other concurrent anticancer treatment
• No other concurrent investigational drugs
• No concurrent participation in another clinical trial