Cetuximab + Best Supportive Care Compared With Best Supportive Care Alone in Metastatic Epidermal Growth Factor Receptor-Positive Colorectal Cancer

RATIONALE: Monoclonal antibodies, such as cetuximab, can target tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Best supportive care is the use of drugs and other treatments to improve the quality of life of patients. Combining cetuximab with best supportive care may slow the growth of the tumor and help patients live longer and more comfortably. It is not yet known whether cetuximab combined with best supportive care is more effective than best supportive care alone in treating metastatic epidermal growth factor receptor-positive colorectal cancer. PURPOSE: This randomized phase III trial is studying cetuximab and best supportive care to see how well they work compared to best supportive care alone in treating patients with metastatic epidermal growth factor receptor-positive colorectal cancer.

Sex

All

Minimum age

16 Years

Maximum age

120 Years

DISEASE CHARACTERISTICS:

* Histologically confirmed colorectal cancer

  * Metastatic disease
* Epidermal growth factor receptor (EGFR)-positive by immunochemistry
* Measurable or evaluable disease
* Not amenable to standard curative therapy

  * Best supportive care is the only available option
* Must have received a prior thymidylate synthase inhibitor (e.g., fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) in the adjuvant or metastatic setting

  * Combination therapy with oxaliplatin or irinotecan allowed
* Must have failed\* a prior regimen containing irinotecan and a prior regimen containing oxaliplatin for metastatic disease OR relapsed within 6 months after an adjuvant regimen containing irinotecan or oxaliplatin OR have documented unsuitability for such regimens
* No symptomatic CNS metastases NOTE: \*Failure is defined as either disease progression (clinical or radiological) or intolerance to the regimen

PATIENT CHARACTERISTICS:

Age

* 16 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* See Disease Characteristics
* Absolute granulocyte count ≥ 1,500/mm\^3
* Platelet count ≥ 75,000/mm\^3
* Hemoglobin ≥ 8.0 g/dL

Hepatic

* AST and ALT ≤ 5 times upper limit of normal (ULN)
* Bilirubin ≤ 2.5 times ULN

Renal

* Creatinine ≤ 1.5 times ULN

Cardiovascular

* No uncontrolled angina
* No arrhythmias
* No cardiomyopathy
* No congestive heart failure
* No myocardial infarction\* within the past 6 months NOTE: \*Pre-treatment ECG as only evidence of infarction is allowed

Pulmonary

* No severe restrictive lung disease
* No interstitial lung disease by chest x-ray

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment
* No active pathological condition that would preclude study participation
* No psychological or geographical condition that would preclude study compliance
* No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior cetuximab
* No prior murine monoclonal antibody therapy (e.g., edrecolomab)

Chemotherapy

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy and recovered
* No concurrent chemotherapy

Radiotherapy

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered
* Concurrent palliative radiotherapy allowed except to index lesions

Surgery

* At least 4 weeks since prior major surgery and recovered

Other

* No prior EGFR-targeted therapy (e.g., erlotinib or gefitinib)
* More than 30 days since prior experimental therapeutic agents
* More than 4 weeks since prior investigational agents
* No concurrent enrollment in another clinical study
* No other concurrent EGFR-targeted therapy
* No other concurrent non-cytotoxic experimental agents

• BACKGROUNDGupta A, O'Callaghan CJ, Zhu L, Jonker DJ, Wong RPW, Colwell B, Moore MJ, Karapetis CS, Tebbutt NC, Shapiro JD, Tu D, Booth CM. Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial. JCO Oncol Pract. 2023 Jun;19(6):e859-e866. doi: 10.1200/OP.22.00737. Epub 2023 Mar 7. PMID 36881786
• RESULTAu HJ, Karapetis CS, O'Callaghan CJ, Tu D, Moore MJ, Zalcberg JR, Kennecke H, Shapiro JD, Koski S, Pavlakis N, Charpentier D, Wyld D, Jefford M, Knight GJ, Magoski NM, Brundage MD, Jonker DJ. Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial. J Clin Oncol. 2009 Apr 10;27(11):1822-8. doi: 10.1200/JCO.2008.19.6048. Epub 2009 Mar 9. PMID 19273701
• RESULTJonker DJ, Karapetis C, Harbison C, et al.: High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): results from NCIC CTG CO.17-A phase III trial of cetuximab versus best supportive care (BSC).. [Abstract] J Clin Oncol 27 (Suppl 15): A-4016, 2009.
• RESULTAsmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-126. doi: 10.1093/annonc/mdq309. Epub 2010 Jul 5. PMID 20603436
• RESULTKarapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. doi: 10.1056/NEJMoa0804385. PMID 18946061
• RESULTMittmann N, Au HJ, Tu D, et al.: A prospective economic analysis of cost-effectiveness of cetuximab for metastatic colorectal cancer patients from the NCIC CTG and AGITG CO.17 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-6528, 2008.