RATIONALE: Drugs used in chemotherapy such as epothilone D work in different ways to stop
tumor cells from dividing so they stop growing or die.
PURPOSE: This phase II trial is studying how well epothilone D works as second-line therapy
in treating patients with advanced or metastatic refractory colorectal cancer.
- Determine the antitumor activity of epothilone D as second-line treatment, in terms of
objective response rate, in patients with advanced or metastatic refractory colorectal
- Determine the safety of this drug in these patients.
- Determine the response duration in patients responding to treatment with this drug.
- Determine time to tumor progression and overall survival in patients treated with this
- Correlate efficacy and safety with plasma concentrations of this drug and its major
metabolites in these patients.
OUTLINE: This is an open-label, multicenter study.
Patients receive epothilone D IV over 90 minutes on days 1, 8, and 15. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 19-69 patients will be accrued for this study.
- Histologically or cytologically confirmed advanced or metastatic adenocarcinoma of
the colon or rectum
- Evidence of at least 1 site of unidimensionally measurable disease by radiography or
- Failed 1 prior treatment with a fluoropyrimidine in combination with either
irinotecan OR oxaliplatin for advanced or metastatic disease
- No known CNS metastases
- 18 and over
- ECOG 0-1
- Not specified
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
- Alkaline phosphatase ≤ 5 times ULN
- Creatinine ≤ 1.5 times ULN
- No New York Heart Association class III or IV congestive heart failure
- No QTc > 450 msec for males or > 470 msec for females
- No personal or family history of congenital long QT syndrome
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No pre-existing neuropathy grade 2 or greater
- No documented grade 3 or 4 hypersensitivity reaction to prior therapy containing
- No infection requiring parenteral or oral anti-infective treatment
- No altered mental status or psychiatric condition that would preclude giving informed
- No other medical condition that would preclude study participation
- No other malignancy within the past 5 years except cured basal cell skin cancer,
carcinoma in situ of the cervix or bladder, or stage T1 or T2 prostate cancer with a
prostate-specific antigen < 2 ng/mL
PRIOR CONCURRENT THERAPY:
- No concurrent sargramostim (GM-CSF)
- No concurrent routine prophylactic use of filgrastim (G-CSF)
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy and recovered
- Not specified
- At least 3 weeks since prior radiotherapy and recovered
- At least 3 weeks since prior surgery and recovered
- More than 3 weeks since prior investigational agents (therapeutic or diagnostic)
- No other concurrent therapy for advanced or metastatic colorectal cancer
- No other concurrent investigational drugs