Clinical trial NCT00077259: Epothilone D as Second-Line Treatment for Patients With Advanced or Metastatic Refractory Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: 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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Leonard B. Saltz, MD
role: STUDY_CHAIR
References: