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

Inclusion Criteria

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