Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin, Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00006015
• Other study ID #: CDR0000068024
• Secondary ID: U10CA031946CALGB
• Status: Terminated
• Phase: Phase 2
• First received: July 5, 2000
• Last updated: May 1, 2013
• Start date: May 2000
• Est. completion date: February 2003

Study information

• Verified date: June 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying combination chemotherapy plus trastuzumab to see how well it works in treating patients with advanced, recurrent, or metastatic colorectal cancer.

Description:

OBJECTIVES:

• Determine the response rate of patients who overexpress HER-2/neu with metastatic colorectal adenocarcinoma who have progressed on at least 1 prior, but no more than 2 prior, chemotherapy regimens for metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and trastuzumab (Herceptin).

• Determine the time to progression of these patients treated with this regimen.

• Determine the overall toxicity of this regimen in these patients.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and 15. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: February 2003
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced, recurrent, or metastatic colorectal adenocarcinoma

• Resected CNS metastases stable greater than 1 month after completion of radiotherapy for CNS metastases eligible

• No existing CNS metastases allowed

• Measurable disease

• At least 1 dimension as at least 20 mm with conventional techniques OR

• At least 10 mm with spiral CT scan

• No truly nonmeasurable lesions:

• Bone lesions

• Leptomeningeal disease

• Lymphangitis cutis/pulmonis

• Abdominal masses not confirmed and followed by imaging techniques

• Cystic lesions

• Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or irinotecan containing treatment regimens for metastatic colorectal cancer

• Must have documented HER-2/neu overexpression by immunohistochemistry staining

• Staining score at least 2+

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm3

• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

• AST no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No history of cardiac ischemia or congestive heart failure

• LVEF at least 50% by ECG or MUGA

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in situ of the cervix unless completed therapy and considered to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

• No prior platinum containing chemotherapy

• At least 3 weeks since prior chemotherapy and recovered

• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• trastuzumab
4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22)

Drug:
• fluorouracil
500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break
• leucovorin calcium
500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break
• oxaliplatin
85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle

Locations

Country	Name	City	State
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of California San Diego Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Rhode Island Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Veterans Affairs Medical Center - Togus	Togus	Maine
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Clark JW, Niedzwiecki D, Hollis D, et al.: Phase II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. [Abstract] Proceedings of the Am

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate		Every 2 tx cycles	No
Primary	Time to progression		Every 2 tx cycles	No
Primary	Overall toxicity		Each cycle during tx	Yes