BMS-247550 in Treating Patients With Metastatic Colorectal Cancer

A Phase II Study Of Epothilone Analog BMS-247550 In Patients With Metastatic Colorectal Cancer Previously Treated With A Fluoropyrimidine And Irinotecan

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of BMS-247550 in treating patients who have metastatic colorectal cancer.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: ixabepilone; Drug: Fluoropyrimidine

Detailed Description

OBJECTIVES:

• Determine the clinical activity of BMS-247550, as measured by the tumor response rate, in patients with metastatic colorectal cancer previously treated with a fluoropyrimidine and irinotecan.
• Determine the safety of this drug in these patients.
• Determine the response duration, time to progression, and survival in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive BMS-247550 IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive up to 4 additional courses of treatment beyond CR.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 19-55 patients will be accrued for this study within 6 months.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Georgia Cancer Specialists

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 metastatic colorectal adenocarcinoma

• Prior treatment for metastatic disease with at least:

  • One regimen of irinotecan in combination with a fluoropyrimidine OR

  • Two regimens comprising fluoropyrimidine-based first-line therapy and irinotecan-based second-line therapy

    • May have received cetuximab and/or a fluoropyrimidine as part of second- line therapy
• Disease progression during or within 4 months of treatment with irinotecan
• At least 1 bidimensionally measurable lesion
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count greater than 125,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 2.5 times ULN (5 times ULN if hepatic metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No history of unstable angina, myocardial infarction, or congestive heart failure within the past 6 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known prior severe hypersensitivity reactions to agents containing Cremophor EL
• No motor or sensory neuropathy grade 2 or greater
• No concurrent serious uncontrolled infection or other nonmalignant medical illness
• No concurrent psychiatric disorders or other conditions that would preclude study compliance
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent immunotherapy
• No growth factors for 24 hours before and after cytotoxic chemotherapy

Chemotherapy:

• See Disease Characteristics
• Additional prior adjuvant or neoadjuvant chemotherapy allowed
• At least 4 weeks since prior chemotherapy and recovered
• No more than 2 prior regimens of cytotoxic chemotherapy for metastatic disease
• No prior oxaliplatin
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except hormone replacement therapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to target lesion unless the lesion has shown progression after completion of radiotherapy

• No concurrent therapeutic radiotherapy

  • Focal radiotherapy for palliation of bone symptoms may be allowed

Surgery:

• At least 1 week since prior minor surgery (3 weeks for major surgery) and recovered

Other:

• No other concurrent experimental anticancer medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-247550	Drug: Irinotecan; Drug: ixabepilone; Drug: Fluoropyrimidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the clinical activity of BMS-247550, as measured by the tumor response rate, in patients with metastatic colorectal cancer previously treated with a fluoropyrimidine and irinotecan.	baseline to survival

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the safety of this drug in these patients.	baseline to survival
Determine the response duration, time to progression, and survival in patients treated with this drug.	baseline to survival

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Andres Forero-Torres, MD, CSU, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: August 5, 2003
• First Posted (Estimate): August 6, 2003

Study Record Updates

• Last Update Posted (Estimate): August 5, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 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
• 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; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CDR0000069272; UAB-0145; BMS-CA163-012; UAB-F011029021; NCI-G02-2051