Epothilone D as Second-Line Treatment for Patients With Advanced or Metastatic Refractory Colorectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary 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 cancer. Secondary 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 drug. 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.

Official Title
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A Phase II Study Of KOS-862 (Epothilone D), Administered Intravenously Weekly For 3 Weeks Every 4 Weeks, In The Second-Line Treatment Of Patients With Advanced Or Metastatic Colorectal Carcinoma (CRC)

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: epothilone D


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 physical examination Failed 1 prior treatment with a fluoropyrimidine in combination with either irinotecan OR oxaliplatin for advanced or metastatic disease No known CNS metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Hemoglobin ≥ 9 g/dL Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic 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 Renal Creatinine ≤ 1.5 times ULN Cardiovascular 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 Other 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 Cremophor No infection requiring parenteral or oral anti-infective treatment No altered mental status or psychiatric condition that would preclude giving informed consent 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: Biologic therapy No concurrent sargramostim (GM-CSF) No concurrent routine prophylactic use of filgrastim (G-CSF) Chemotherapy See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered Endocrine therapy Not specified Radiotherapy At least 3 weeks since prior radiotherapy and recovered Surgery At least 3 weeks since prior surgery and recovered Other 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: epothilone D|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent colon cancer, recurrent rectal cancer, stage III colon cancer, stage III rectal cancer, stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum