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

NCT00077233 | Terminated Phase 3

• 3 other identifiers: CALGB 80203U10CA031946CDR0000350016
• Study Type: interventional
• Target: 238
• Locations: 1 country
• Sites: 77

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; adenocarcinoma of the rectum; recurrent colon cancer; recurrent rectal cancer; stage IV colon cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Up to 3 years of follow up

Secondary Outcomes (7)

• Progression-free survival

  Up to 18 months of follow up

• Complete response

  Up to 18 months of follow up

• Partial response

  Up to 18 months of follow up

• Proportion of patients experiencing ≥ Grade 3 diarrhea

  Up to 30 days post-treatment

• Proportion of patients experiencing ≥ Grade 3 ANC

  Up to 30 days post-treatment

Study Arms (4)

Arm A: FOLFIRI

ACTIVE COMPARATOR

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.

Drug: 5-FU; Drug: irinotecan; Drug: leucovorin

Arm B: FOLFIRI + C225

EXPERIMENTAL

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.

Drug: cetuximab; Drug: 5-FU; Drug: irinotecan; Drug: leucovorin

Arm C: FOLFOX

ACTIVE COMPARATOR

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.

Drug: 5-FU; Drug: leucovorin; Drug: oxaliplatin

Arm D: FOLFOX + C225

EXPERIMENTAL

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.

Drug: cetuximab; Drug: 5-FU; Drug: leucovorin; Drug: oxaliplatin

Interventions

cetuximab DRUG

IV

Also known as: C225

Arm B: FOLFIRI + C225; Arm D: FOLFOX + C225

5-FU DRUG

IV

Also known as: 5-fluorouracil

Arm A: FOLFIRI; Arm B: FOLFIRI + C225; Arm C: FOLFOX; Arm D: FOLFOX + C225

irinotecan DRUG

IV

Also known as: CPT-11

Arm A: FOLFIRI; Arm B: FOLFIRI + C225

leucovorin DRUG

IV

Also known as: calcium folinate

Arm A: FOLFIRI; Arm B: FOLFIRI + C225; Arm C: FOLFOX; Arm D: FOLFOX + C225

oxaliplatin DRUG

IV

Also known as: Eloxatin

Arm C: FOLFOX; Arm D: FOLFOX + C225

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

1. Locally Advanced or Metastatic Colorectal Cancer * Eligible patients must have histologically or cytologically documented locally advanced or metastatic colorectal cancer. The site of the primary lesion must be or have been confirmed endoscopically, surgically or radiologically to have been in the large bowel. * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Bristol-Myers Squibb: collaborator
• Eli Lilly and Company: collaborator

Study Sites (77)

Northeast Alabama Regional Medical Center

Anniston, Alabama, 36207, United States

Location

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

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

Los Angeles, California, 90048, United States

Location

Naval Medical Center - San Diego

San Diego, California, 92134-3202, United States

Location

Veterans Affairs Medical Center - San Diego

San Diego, California, 92161, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Veterans Affairs Medical Center - San Francisco

San Francisco, California, 94121, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5001, United States

Location

Veterans Affairs Medical Center - Washington, DC

Washington D.C., District of Columbia, 20422, United States

Location

Broward General Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Memorial Regional Cancer Center at Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Palm Beach Cancer Institute

West Palm Beach, Florida, 33401, United States

Location

MBCCOP - University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, 60612, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Louis A. Weiss Memorial Hospital

Chicago, Illinois, 60640, United States

Location

CCOP - Evanston

Evanston, Illinois, 60201, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615-7828, United States

Location

West Suburban Center for Cancer Care

River Forest, Illinois, 60305, United States

Location

Fort Wayne Medical Oncology and Hematology, Incorporated

Fort Wayne, Indiana, 46885-5099, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1009, United States

Location

Baptist Hospital East - Louisville

Louisville, Kentucky, 40207, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

UMASS Memorial Cancer Center - University Campus

Worcester, Massachusetts, 01655, United States

Location

Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, 55417, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, 65201, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

CCOP - Kansas City

Kansas City, Missouri, 64131, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Missouri Baptist Cancer Center

St Louis, Missouri, 63131, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Veterans Affairs Medical Center - Las Vegas

Las Vegas, Nevada, 89106, United States

Location

New Hampshire Oncology-Hematology, PA - Hooksett

Hooksett, New Hampshire, 03106, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, 14215, United States

Location

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

East Syracuse, New York, 13057, United States

Location

Queens Cancer Center of Queens Hospital

Jamaica, New York, 11432, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

New York Weill Cornell Cancer Center at Cornell University

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, 13210, United States

Location

Veterans Affairs Medical Center - Asheville

Asheville, North Carolina, 28805, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

NorthEast Oncology Associates - Concord

Concord, North Carolina, 28025, United States

Location

Veterans Affairs Medical Center - Durham

Durham, North Carolina, 27705, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cape Fear Valley Health System

Fayetteville, North Carolina, 28302-2000, United States

Location

CCOP - Southeast Cancer Control Consortium

Goldsboro, North Carolina, 27534-9479, United States

Location

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, 28374, United States

Location

Zimmer Cancer Center at New Hanover Regional Medical Center

Wilmington, North Carolina, 28402-9025, United States

Location

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, 27157-1082, United States

Location

Arthur G. James Cancer Hospital at Ohio State University

Columbus, Ohio, 43210-1240, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Lifespan: The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Veterans Affairs Medical Center - Dallas

Dallas, Texas, 75219, United States

Location

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

Dallas, Texas, 75390-8852, United States

Location

Vermont Cancer Center at University of Vermont

Burlington, Vermont, 05401-3498, United States

Location

Martha Jefferson Hospital

Charlottesville, Virginia, 22902, United States

Location

Virginia Oncology Associates - Norfolk

Norfolk, Virginia, 23502, United States

Location

MBCCOP - Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke

Roanoke, Virginia, 24014, United States

Location

St. Mary's Medical Center

Huntington, West Virginia, 25701, United States

Location

Related Publications (2)

• 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.

  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.

  RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Alan Venook, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2004
• First Posted: February 11, 2004
• Study Start: December 1, 2003
• Primary Completion: December 1, 2006
• Study Completion: June 1, 2010
• Last Updated: May 16, 2018

Record last verified: 2018-05

Locations

US (77)