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Colorectal CancerPhase 3NCT00077233

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

A Phase 3 study testing cetuximab, 5-FU and irinotecan in people with Colorectal Cancer, run by Alliance for Clinical Trials in Oncology at 77 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
cetuximab, 5-FU and irinotecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
238 participants
Where
77 sitesUnited States
Study dates
Dec 2003to Jun 2010
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  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.
  1. 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.
  1. 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.
  2. 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.
  3. 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.
  4. Age ≥ 18 years
  5. CTC (ECOG) performance status of 0-1.
  6. 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.
  7. Patients must have at least one paraffin block available or appropriate number of unstained slides for analysis of EGFR status.
  8. No symptomatic sensory peripheral neuropathy of ≥ grade II at baseline.
  9. 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.
  1. No known central nervous system metastases or carcinomatous meningitis.
  2. No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
  3. No pleural effusion or ascites that causes ≥ grade 2 dyspnea.
  4. 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.
  5. No prior exposure or known sensitivity to chimerized or murine antibodies, C225 (or other EGFR inhibitors) or any tyrosine kinase inhibitors
  6. 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.
  7. Patients must not have an uncontrolled seizure disorder, or active neurological disease.
  8. Patients may not have received itraconazole or ketoconazole less than 4 weeks prior to registration.
  9. 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

Trial locations and contacts

77 sites in 1 country.

77 sites in 1 country

United States77 sites

  • Northeast Alabama Regional Medical Center

    Anniston, Alabama, 36207

  • Veterans Affairs Medical Center - Asheville

    Asheville, North Carolina, 28805

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

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

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Veterans Affairs Medical Center - Buffalo

    Buffalo, New York, 14215

  • Vermont Cancer Center at University of Vermont

    Burlington, Vermont, 05401-3498

  • Cooper University Hospital

    Camden, New Jersey, 08103

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

    Chapel Hill, North Carolina, 27599-7295

  • Martha Jefferson Hospital

    Charlottesville, Virginia, 22902

  • MBCCOP - University of Illinois at Chicago

    Chicago, Illinois, 60612

  • Veterans Affairs Medical Center - Chicago (Westside Hospital)

    Chicago, Illinois, 60612

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Louis A. Weiss Memorial Hospital

    Chicago, Illinois, 60640

  • Veterans Affairs Medical Center - Columbia (Truman Memorial)

    Columbia, Missouri, 65201

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • Arthur G. James Cancer Hospital at Ohio State University

    Columbus, Ohio, 43210-1240

  • NorthEast Oncology Associates - Concord

    Concord, North Carolina, 28025

  • Veterans Affairs Medical Center - Dallas

    Dallas, Texas, 75219

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

    Dallas, Texas, 75390-8852

  • Veterans Affairs Medical Center - Durham

    Durham, North Carolina, 27705

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

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

    East Syracuse, New York, 13057

  • CCOP - Evanston

    Evanston, Illinois, 60201

  • Cape Fear Valley Health System

    Fayetteville, North Carolina, 28302-2000

  • Broward General Medical Center

    Fort Lauderdale, Florida, 33316

  • Fort Wayne Medical Oncology and Hematology, Incorporated

    Fort Wayne, Indiana, 46885-5099

  • CCOP - Southeast Cancer Control Consortium

    Goldsboro, North Carolina, 27534-9479

  • Memorial Regional Cancer Center at Memorial Regional Hospital

    Hollywood, Florida, 33021

  • New Hampshire Oncology-Hematology, PA - Hooksett

    Hooksett, New Hampshire, 03106

  • St. Mary's Medical Center

    Huntington, West Virginia, 25701

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1009

  • Queens Cancer Center of Queens Hospital

    Jamaica, New York, 11432

  • CCOP - Kansas City

    Kansas City, Missouri, 64131

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • CCOP - Southern Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Veterans Affairs Medical Center - Las Vegas

    Las Vegas, Nevada, 89106

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

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

    Los Angeles, California, 90048

  • Baptist Hospital East - Louisville

    Louisville, Kentucky, 40207

  • CCOP - North Shore University Hospital

    Manhasset, New York, 11030

  • North Shore University Hospital

    Manhasset, New York, 11030

  • CCOP - Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Veterans Affairs Medical Center - Minneapolis

    Minneapolis, Minnesota, 55417

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • Mount Sinai Medical Center

    New York, New York, 10029

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

  • Virginia Oncology Associates - Norfolk

    Norfolk, Virginia, 23502

  • Oklahoma University Medical Center

    Oklahoma City, Oklahoma, 73104

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-7680

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • CCOP - Illinois Oncology Research Association

    Peoria, Illinois, 61615-7828

  • FirstHealth Moore Regional Hospital

    Pinehurst, North Carolina, 28374

  • Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania, 15224

  • Lifespan: The Miriam Hospital

    Providence, Rhode Island, 02906

  • MBCCOP - Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • West Suburban Center for Cancer Care

    River Forest, Illinois, 60305

  • Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke

    Roanoke, Virginia, 24014

  • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph

    Saint Joseph, Michigan, 49085

  • Naval Medical Center - San Diego

    San Diego, California, 92134-3202

  • Veterans Affairs Medical Center - San Diego

    San Diego, California, 92161

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94115

  • Veterans Affairs Medical Center - San Francisco

    San Francisco, California, 94121

  • CCOP - Northern Indiana CR Consortium

    South Bend, Indiana, 46601

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Missouri Baptist Cancer Center

    St Louis, Missouri, 63131

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Veterans Affairs Medical Center - Syracuse

    Syracuse, New York, 13210

  • Lombardi Cancer Center at Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Walter Reed Army Medical Center

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

  • Veterans Affairs Medical Center - Washington, DC

    Washington D.C., District of Columbia, 20422

  • Palm Beach Cancer Institute

    West Palm Beach, Florida, 33401

  • Zimmer Cancer Center at New Hanover Regional Medical Center

    Wilmington, North Carolina, 28402-9025

  • Comprehensive Cancer Center at Wake Forest University

    Winston-Salem, North Carolina, 27157-1082

  • UMASS Memorial Cancer Center - University Campus

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Phase II Trial Of Irinotecan /5-FU/ Leucovorin Or Oxaliplatin /5-FU / Leucovorin With And Without Cetuximab (C225) For Patients With Untreated Metastatic Adenocarcinoma Of The Colon or Rectum

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.

Read the detailed description

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.

Keywords
adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer, stage IV colon cancer, stage IV rectal cancer
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00077233
Study groupRoleWhat they receive
Arm A: FOLFIRIActive comparatorPatients 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.
Receives: Drug: 5-FU; Drug: irinotecan; Drug: leucovorin
Arm B: FOLFIRI + C225ExperimentalPatients 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.
Receives: Drug: cetuximab; Drug: 5-FU; Drug: irinotecan; Drug: leucovorin
Arm C: FOLFOXActive comparatorPatients 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.
Receives: Drug: 5-FU; Drug: leucovorin; Drug: oxaliplatin
Arm D: FOLFOX + C225ExperimentalPatients 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.
Receives: Drug: cetuximab; Drug: 5-FU; Drug: leucovorin; Drug: oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Measured: Up to 3 years of follow up

Secondary outcomes (7)

  1. Progression-free survival

    Measured: Up to 18 months of follow up

  2. Complete response

    Measured: Up to 18 months of follow up

  3. Partial response

    Measured: Up to 18 months of follow up

  4. Proportion of patients experiencing ≥ Grade 3 diarrhea

    Measured: Up to 30 days post-treatment

  5. Proportion of patients experiencing ≥ Grade 3 ANC

    Measured: Up to 30 days post-treatment

  6. Percent of total dose administered

    Measured: Up to 30 days post-treatment

  7. Proportion of patients experiencing ≥ Grade 4 toxicity on each cetuximab treatment arm

    Measured: Up to 30 days post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2004 (estimated)
  2. Study startDec 2003
  3. Primary completionDec 2006
  4. Study completionJun 2010

Why it stopped: Poor accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
238 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00077233
Sponsor's protocol ID
CALGB 80203
Other IDs
U10CA031946, CDR0000350016
Status last verified
May 2018
First submitted
10 Feb 2004
Last updated
16 May 2018
Results posted
No
Data monitoring committee
No

Publications

  • 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.

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cetuximab, 5-FU and irinotecan in people with Colorectal Cancer, run by Alliance for Clinical Trials in Oncology at 77 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Up to 3 years of follow up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00077233, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2018.

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