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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00077259

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: epothilone D	Phase 2

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 Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Study Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Sep 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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