RATIONALE: SU011248 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well SU011248 works in treating patients with metastatic colorectal adenocarcinoma (cancer) that has not responded to previous treatment with irinotecan, oxaliplatin, and a fluoropyrimidine (such as fluorouracil) with or without bevacizumab.

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum recurrent colon cancer recurrent rectal cancer	Drug: SU011248  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Leonard Bruce Saltz, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000360732; MSKCC-03143; PFIZER-A6181003; PFIZER-PHA-RTKC-0511; NCT00082771
Record last reviewed:  April 2004
Last Updated:  March 10, 2005
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00082771
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08