BMS-247550 in Treating Patients With Metastatic Colorectal Cancer

A Phase II Study Of Epothilone Analog BMS-247550 In Patients With Metastatic Colorectal Cancer Previously Treated With A Fluoropyrimidine And Irinotecan

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of BMS-247550 in treating patients who have metastatic colorectal cancer.

OBJECTIVES:

• Determine the clinical activity of BMS-247550, as measured by the tumor response rate, in patients with metastatic colorectal cancer previously treated with a fluoropyrimidine and irinotecan.
• Determine the safety of this drug in these patients.
• Determine the response duration, time to progression, and survival in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive BMS-247550 IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive up to 4 additional courses of treatment beyond CR.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 19-55 patients will be accrued for this study within 6 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic colorectal adenocarcinoma

• Prior treatment for metastatic disease with at least:

  • One regimen of irinotecan in combination with a fluoropyrimidine OR

  • Two regimens comprising fluoropyrimidine-based first-line therapy and irinotecan-based second-line therapy

    • May have received cetuximab and/or a fluoropyrimidine as part of second- line therapy

• Disease progression during or within 4 months of treatment with irinotecan

• At least 1 bidimensionally measurable lesion

• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count greater than 125,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 2.5 times ULN (5 times ULN if hepatic metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No history of unstable angina, myocardial infarction, or congestive heart failure within the past 6 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known prior severe hypersensitivity reactions to agents containing Cremophor EL
• No motor or sensory neuropathy grade 2 or greater
• No concurrent serious uncontrolled infection or other nonmalignant medical illness
• No concurrent psychiatric disorders or other conditions that would preclude study compliance
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent immunotherapy
• No growth factors for 24 hours before and after cytotoxic chemotherapy

Chemotherapy:

• See Disease Characteristics
• Additional prior adjuvant or neoadjuvant chemotherapy allowed
• At least 4 weeks since prior chemotherapy and recovered
• No more than 2 prior regimens of cytotoxic chemotherapy for metastatic disease
• No prior oxaliplatin
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except hormone replacement therapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

• No prior radiotherapy to target lesion unless the lesion has shown progression after completion of radiotherapy

• No concurrent therapeutic radiotherapy

  • Focal radiotherapy for palliation of bone symptoms may be allowed

Surgery:

• At least 1 week since prior minor surgery (3 weeks for major surgery) and recovered

Other:

• No other concurrent experimental anticancer medications