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

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)

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: epothilone D

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): September 1, 2004

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 10, 2004
• First Posted (Estimate): February 11, 2004

Study Record Updates

• Last Update Posted (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Epothilones; Desoxyepothilone B
• Other Study ID Numbers: 03-113; MSKCC-03113; ROCHE-NO17320