Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI, Pharmaceutical / Industry MSKCC-03113 ROCHE-NO17320, NCT00077259

Objectives

Primary

1. 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

1. Determine the safety of this drug in these patients.
2. Determine the response duration in patients responding to treatment with this drug.
3. Determine time to tumor progression and overall survival in patients treated with this drug.
4. Correlate efficacy and safety with plasma concentrations of this drug and its major metabolites in these patients.

Entry Criteria

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

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

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/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

A total of 19-69 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Saltz, MD, Protocol chair		Ph: 212-639-2501; 800-525-2225

Registry Information
Official Title		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)
Trial Start Date		2003-10-14
Registered in ClinicalTrials.gov		NCT00077259
Date Submitted to PDQ		2003-12-16
Information Last Verified		2005-04-06
NCI Grant/Contract Number		P30-CA08748