BMS-247550 in Treating Patients With Recurrent or Metastatic Colorectal Cancer

A Phase II Study Of Epothilone B Analog BMS-247550 (NSC 710428D) In Patients With Advanced Colorectal Carcinoma

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 recurrent or metastatic colorectal cancer.

OBJECTIVES:

• Determine the objective response rate in patients with locally recurrent or metastatic colorectal cancer treated with BMS-247550.
• Determine the toxicity of this drug in these patients.
• Determine the duration of response, median and overall survival, and time to progression in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive BMS-247550 IV over 3 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 weeks.

PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study within 8-10 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic or locally recurrent adenocarcinoma of the colon or rectum that is not amenable to potentially curative surgical resection

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • The following are not considered measurable lesions:

    • Lesions seen on colonoscopic examination or barium study
    • Bone metastases
    • CNS lesions
    • Ascites

• Failed prior combination therapy comprising fluorouracil, leucovorin calcium, and irinotecan for metastatic disease

• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT/AST no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 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
• No grade 2 or greater peripheral neuropathy
• No history of allergic hypersensitivity reaction to compounds containing polyoxyethylated castor oil (Cremophor EL) (e.g., paclitaxel or compounds of similar chemical or biological composition to BMS-247550)
• No other currently active malignancy (less than 30% risk of relapse and completed prior therapy) except non-melanoma skin cancer or carcinoma in situ of the cervix
• No uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy
• No concurrent colony-stimulating factors during first course of therapy

Chemotherapy:

• See Disease Characteristics
• Prior adjuvant chemotherapy allowed
• At least 4 weeks since prior cytotoxic chemotherapy and recovered
• No more than 1 prior chemotherapy regimen for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent anticancer hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent therapeutic radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery

Other:

• At least 30 days since prior investigational agents
• At least 7 days since prior cimetidine
• No other concurrent anticancer investigational agents, commercial agents, or therapies
• No concurrent unconventional therapy, food, or vitamin supplement containing Hypericum perforatum (St. John's Wort)
• No concurrent cimetidine
• No concurrent combination antiretroviral therapy for HIV-positive patients