FOLFIRI or FOLFOX With or Without Cetuximab in Patients With Metastatic Adenocarcinoma of the Colon or Rectum

NCT ID: NCT00077233

Last Updated: 2018-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

238 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2010-06-30

Brief Summary

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This is a randomized phase II study trial that has served as a screening trial to test the increased efficacy of chemotherapy + cetuximab versus chemotherapy alone among patients with untreated, advanced or metastatic colon cancer regardless of tumor status with respect to EGFR.

Detailed Description

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CALGB 80203 was activated on December 15, 2003. In February 2004, based on the results of the randomized trial of IFL +/- cetuximab showing a significant improvement in overall survival with cetuximab, cetuximab was approved by the FDA for use as front-line therapy for patients with metastatic colon cancer. In response to this action, the Data Safety and Monitoring Board recommended closure of CALGB 80203. CALGB 80203 was subsequently closed to accrual in January 2005 with 238 of the originally targeted 2200 patients enrolled. A final decision was to "replace" CALGB 80203 with a three-treatment arm randomized trial of chemotherapy (FOLFOX or FOLFIRI) with and without cetuximab and/or bevacizumab. The protocol was amended to allow analysis of the data from CALGB 80203 as a randomized phase II trial and reporting of the results.

Patients were stratified according to prior adjuvant chemotherapy (yes vs no) and prior pelvic radiation (yes vs no). Patients must have completed any major surgery or radiotherapy (eg, chest or bone palliative RT or pelvic RT) ≥ 4 weeks from registration and completed any minor surgery ≥ 2 weeks from registration. Patients must have fully recovered from the procedure and/or radiotherapy. Patients must have initiated treatment within 7 days of registration. Patients were randomized to 1 of 4 treatment arms, please see a description of the treatment regimens in the "Arms" section. In addition, patients received concomitant and supportive therapy as appropriate per the protocol.

OBJECTIVES:

Primary

1\. To determine if the addition of C225 to FOLFIRI or FOLFOX chemotherapy prolongs survival of patients with untreated, advanced or metastatic colorectal cancer.

Secondary

1. To determine if the FOLFIRI and FOLFOX regimens are equivalent in terms of survival as front-line therapy for advanced colorectal patients.
2. To determine the level of EGFR expression in patients with metastatic colorectal cancer.

Patients were followed up to 3 years post-treatment.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: FOLFIRI

Patients receive irinotecan 180 mg/m\^2 over 90 minutes on day 1, then leucovorin 400 mg/m\^2 over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks.

Group Type ACTIVE_COMPARATOR

5-FU

Intervention Type DRUG

IV

irinotecan

Intervention Type DRUG

IV

leucovorin

Intervention Type DRUG

IV

Arm B: FOLFIRI + C225

Patients receive irinotecan 180 mg/m\^2 over 90 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.

Group Type EXPERIMENTAL

cetuximab

Intervention Type DRUG

IV

5-FU

Intervention Type DRUG

IV

irinotecan

Intervention Type DRUG

IV

leucovorin

Intervention Type DRUG

IV

Arm C: FOLFOX

Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks.

Group Type ACTIVE_COMPARATOR

5-FU

Intervention Type DRUG

IV

leucovorin

Intervention Type DRUG

IV

oxaliplatin

Intervention Type DRUG

IV

Arm D: FOLFOX + C225

Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.

Group Type EXPERIMENTAL

cetuximab

Intervention Type DRUG

IV

5-FU

Intervention Type DRUG

IV

leucovorin

Intervention Type DRUG

IV

oxaliplatin

Intervention Type DRUG

IV

Interventions

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cetuximab

IV

Intervention Type DRUG

5-FU

IV

Intervention Type DRUG

irinotecan

IV

Intervention Type DRUG

leucovorin

IV

Intervention Type DRUG

oxaliplatin

IV

Intervention Type DRUG

Other Intervention Names

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C225 5-fluorouracil CPT-11 calcium folinate Eloxatin

Eligibility Criteria

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Inclusion Criteria

* Patients with a history of colorectal cancer treatment by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless:

* Either an interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease OR
* The primary cancer was stage I.
* Clinicians should consider biopsy of lesions to establish the diagnosis of metastatic colorectal cancer in each case if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
2. No prior treatment for advanced or metastatic colorectal cancer

* Patients may have received prior adjuvant chemotherapy (no more than 6 months or 4 cycles) or radiation with radiosensitizing chemotherapy. The last course of chemotherapy must have concluded \> 12 months prior to registration. Patients may not have previously received irinotecan ≤ or oxaliplatin therapy in either the adjuvant or metastatic setting. No concurrent use of additional investigational agents is allowed while participating in this study.
3. Patients may not have had prior radiotherapy to greater than 25% of bone marrow.

Standard adjuvant rectal cancer chemoradiation will not exclude the patient from protocol entry. Radiation must have concluded ≥ 4 weeks from registration.
4. Patients should have completed any major surgery ≥ 4 weeks from registration. Patients must have completed any minor surgery ≥ 2 weeks from registration. Patients must have fully recovered from the procedure. Insertion of a vascular access device is not considered major or minor surgery.
5. No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for five years.
6. Age ≥ 18 years
7. CTC (ECOG) performance status of 0-1.
8. No evidence of Gilbert's syndrome - Patients with Gilbert's Syndrome may have a greater risk of irinotecan toxicity due to the abnormal glucuronidation of SN-38. Evidence of Gilbert's Syndrome would include a prior finding of an isolated elevation of indirect bilirubin.
9. Patients must have at least one paraffin block available or appropriate number of unstained slides for analysis of EGFR status.
10. No symptomatic sensory peripheral neuropathy of ≥ grade II at baseline.
11. Non-pregnant and non-lactating

* Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG within 72 hours prior to initiation of treatment. This is because DNA alkylating agents are known to be teratogenic, and the effects of irinotecan, OXAL, 5-FU and C225 on a developing fetus at the recommended therapeutic doses are unknown.
* Women of child bearing potential includes:

* any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or
* is not postmenopausal \[defined as amenorrhea ≥ 12 consecutive months\] or
* women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL
* women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), should be considered to be of child bearing potential.
* Should a woman become pregnant or suspect she is pregnant while participating on on this study, she should inform her physician immediately. Because the risk of toxicity of these agents in nursing infants is also unknown, breastfeeding should be discontinued.
12. No known central nervous system metastases or carcinomatous meningitis.
13. No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
14. No pleural effusion or ascites that causes ≥ grade 2 dyspnea.
15. No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of \> 3 watery or soft stools daily in patients without a colostomy or ileostomy. Patients with a colostomy or ileostomy may be entered at investigator discretion.
16. No prior exposure or known sensitivity to chimerized or murine antibodies, C225 (or other EGFR inhibitors) or any tyrosine kinase inhibitors
17. No significant history of cardiac disease, such as unstable angina, CHF, MI, stroke or a LVEF below the institutional range of normal on a baseline multiple gated acquisition (MUGA) or echocardiogram.
18. Patients must not have an uncontrolled seizure disorder, or active neurological disease.
19. Patients may not have received itraconazole or ketoconazole less than 4 weeks prior to registration.
20. Required Initial Laboratory Values:

* Granulocytes ≥ 1500/ µl
* Hemoglobin ≥ 9.0 gram/dL (patient may be transfused to meet this criterion)
* Platelet count ≥ 100,000/ µl
* Creatinine ≤ 1.5 x Upper limits of normal (ULN)
* Bilirubin ≤ 1.5 mg/dL
* AST ≤ 5.0 x ULN
* Albumin ≥ 2.5 gram/dL
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan Venook, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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Northeast Alabama Regional Medical Center

Anniston, Alabama, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Naval Medical Center - San Diego

San Diego, California, United States

Site Status

Veterans Affairs Medical Center - San Diego

San Diego, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

Veterans Affairs Medical Center - Washington, DC

Washington D.C., District of Columbia, United States

Site Status

Broward General Medical Center

Fort Lauderdale, Florida, United States

Site Status

Memorial Regional Cancer Center at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

Palm Beach Cancer Institute

West Palm Beach, Florida, United States

Site Status

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

Site Status

CCOP - Evanston

Evanston, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

West Suburban Center for Cancer Care

River Forest, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology, Incorporated

Fort Wayne, Indiana, United States

Site Status

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Baptist Hospital East - Louisville

Louisville, Kentucky, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, United States

Site Status

Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph

Saint Joseph, Michigan, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Missouri Baptist Cancer Center

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Veterans Affairs Medical Center - Las Vegas

Las Vegas, Nevada, United States

Site Status

New Hampshire Oncology-Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

East Syracuse, New York, United States

Site Status

Queens Cancer Center of Queens Hospital

Jamaica, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Asheville

Asheville, North Carolina, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

NorthEast Oncology Associates - Concord

Concord, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Cape Fear Valley Health System

Fayetteville, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Goldsboro, North Carolina, United States

Site Status

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, United States

Site Status

Zimmer Cancer Center at New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital at Ohio State University

Columbus, Ohio, United States

Site Status

Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Lifespan: The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Veterans Affairs Medical Center - Dallas

Dallas, Texas, United States

Site Status

Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Vermont Cancer Center at University of Vermont

Burlington, Vermont, United States

Site Status

Martha Jefferson Hospital

Charlottesville, Virginia, United States

Site Status

Virginia Oncology Associates - Norfolk

Norfolk, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke

Roanoke, Virginia, United States

Site Status

St. Mary's Medical Center

Huntington, West Virginia, United States

Site Status

Countries

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United States

References

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Meyerhardt JA, Jackson McCleary N, Niedzwiecki D, et al.: Impact of age and comorbidities on treatment effect, tolerance, and toxicity in metastatic colorectal cancer (mCRC) patients treated on CALGB 80203. [Abstract] J Clin Oncol 27 ( Suppl 15): A-4038, 2009.

Reference Type RESULT

Venook A, Niedzwiecki D, Hollis D, et al.: Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. [Abstract] J Clin Oncol 24 (Suppl 18): A-3509, 2006.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000350016

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB 80203

Identifier Type: -

Identifier Source: org_study_id

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