Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the colon, stage IV colon cancer, adenocarcinoma of the rectum, stage IV rectal cancer, stage III colon cancer, stage III rectal cancer, recurrent colon cancer, recurrent rectal cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of colorectal adenocarcinoma, defined by 1 of the following:
- Prior or current histologically confirmed primary adenocarcinoma of colon or rectum with clinical or radiological evidence of advanced and/or metastatic disease
- Histologically and cytologically confirmed metastatic adenocarcinoma with clinical and/or radiological evidence of colorectal primary tumor
- Unidimensionally measurable disease by RECIST criteria
Inoperable metastatic or locoregional disease
Potentially resectable liver metastases allowed provided the following criteria are met:
- Fewer than 4 unilobar liver metastases, each < 4 cm in size and without major vascular involvement
- No combination chemotherapy allowed prior to the planned resection of operable liver metastases
- No confirmed K-ras mutation of tumor after screening
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Must be considered fit to undergo combination chemotherapy
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 2.5 times ULN
- Creatinine clearance ≥ 50mL/min OR glomerular filtration rate ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No severe uncontrolled concurrent medical illness (including poorly controlled angina or myocardial infarction within the past 12 weeks) likely to interfere with protocol treatments
- No psychiatric or neurological condition that would preclude study compliance with oral medication or giving informed consent
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No prior or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with COIN-B treatment or assessment of response
- No patients with known hypersensitivity reactions to any of the components of the study treatments
- No proven dihydropyrimidine dehydrogenase deficiency (DPD) or personal or family history of DPD
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior systemic palliative chemotherapy for metastatic disease
- No prior oxaliplatin
- More than 1 month since prior adjuvant chemotherapy comprising fluorouracil (with or without leucovorin calcium), capecitabine, or irinotecan hydrochloride
- More than 1 month since prior chemoradiotherapy comprising fluorouracil (with or without leucovorin calcium) or capecitabine for rectal cancer
- No ongoing requirement for contraindicated concurrent medication
- No concurrent enrollment in any type of study other than observational studies
Sites / Locations
- Bank of Cyprus Oncology Centre
- Bradford Royal Infirmary
- Gloucestershire Oncology Centre at Cheltenham General Hospital
- Essex County Hospital
- Dorset County Hospital
- St. Luke's Cancer Centre at Royal Surrey County Hospital
- Hammersmith Hospital
- St. Mary's Hospital
- Churchill Hospital
- Peterborough Hospitals Trust
- University Hospital of North Staffordshire
- Singleton Hospital
- Royal United Hospital
- Royal Bournemouth Hospital
- Addenbrookes Hospital
- Darent Valley Hospital
- Hereford County Hospital
- Charing Cross Hospital
- Guys and St Thomas' hospitals
- Dorset Cancer Centre, Poole Hospital
- Weston Park
- Southport and Ormskirk
- St Helens and Whiston hospitals
- Warrington and Halton Hospitals
- Worcestershire Royal Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
D
E
Intermittent chemotherapy plus intermittent cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period off all therapy, with reintroduction of the same chemotherapy and cetuximab regimen for a further 12 weeks after initial progression off treatment
Intermittent chemotherapy plus continuous cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period of withdrawal of the chemotherapy, but continued weekly cetuximab monotherapy (maintenance cetuximab), with reintroduction of the same chemotherapy regimen to the cetuximab for a further 12 weeks after initial progression off chemotherapy treatment