RATIONALE: Drugs used in chemotherapy, such as SB-715992, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized phase II trial is studying how well SB-715992 works in treating patients with advanced or metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
recurrent colon cancer stage III colon cancer stage IV colon cancer recurrent rectal cancer stage III rectal cancer Stage IV rectal cancer	Drug: SB-715992  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine objective response rate in patients with advanced or metastatic colorectal cancer treated with 2 different schedules of SB-715992.

Secondary

• Determine time to tumor progression, progression-free survival, and overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine cytoskeletal morphology changes in the cells and tumors of patients treated with this drug.
• Determine the frequency of genomic polymorphisms in genes targeted by this drug and correlate germline polymorphisms of genes targeted by this drug with toxicity and clinical outcome in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive SB-715992 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 24-76 patients (12-38 per treatment arm) will be accrued for this study within 3-12 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer
• Advanced or metastatic disease
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Received prior fluorouracil, irinotecan, oxaliplatin, cetuximab, or bevacizumab
• Received at least 1 chemotherapy regimen for advanced disease
• Tumor accessible for biopsy OR paraffin embedded tissue available
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 50-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drug
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent anticancer biologic therapy

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• No concurrent anticancer hormonal therapy
• Concurrent hormone replacement therapy allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery

• Not specified

Other

• More than 28 days since prior investigational agents
• More than 14 days since prior and no concurrent administration of any of the following CYP3A4 inducers or inhibitors:
• Clarithromycin
• Erythromycin
• Troleandomycin
• Itraconazole
• Ketoconazole
• Fluconazole (dose > 200 mg/day)
• Voriconazole
• Nefazodone
• Fluvoxamine
• Verapamil
• Diltiazem
• Grapefruit juice
• Bitter orange
• Phenytoin
• Carbamazepine
• Phenobarbital
• Oxcarbazepine
• Rifampin
• Rifabutin
• Rifapentine
• Hypericum perforatum (St. John’s wort)
• Modafinil
• More than 6 months since prior and no concurrent amiodarone
• No more than 2 prior therapy regimens for metastatic disease
• No other concurrent anticancer therapy
• No other concurrent cytotoxic therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      City of Hope Medical Group, Pasadena,  California,  91105,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Syma Iqbal, MD,  Study Chair,  University of Southern California   

Study ID Numbers:  CDR0000409586; CCC-PHII-51; NCI-6800; NCT00103311
Record last reviewed:  January 2005
Last Updated:  February 15, 2005
Record first received:  February 7, 2005
ClinicalTrials.gov Identifier:  NCT00103311
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08