Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Medical Research Council.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Cheryl Pugh, Medical Research Council
ClinicalTrials.gov Identifier:
NCT00640081
First received: March 19, 2008
Last updated: February 23, 2012
Last verified: February 2012
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving combination chemotherapy together with intermittent cetuximab is more effective than combination chemotherapy given together with continuous cetuximab in treating colorectal cancer.

PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with intermittent cetuximab to see how well it works compared to combination chemotherapy given together with continuous cetuximab as first-line therapy in treating patients with advanced or metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: cetuximab
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two-arm Phase II Randomised Trial of Intermittent Chemotherapy Plus Continuous Cetuximab and of Intermittent Chemotherapy Plus Intermittent Cetuximab in First Line Treatment of Patients With K-ras-normal (Wild-type) Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Medical Research Council:

Primary Outcome Measures:
  • Failure-free survival at 10 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions [ Designated as safety issue: Yes ]
  • Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rates at 12, 24, and 36 weeks [ Designated as safety issue: No ]
  • Toxicity of each treatment regimen by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Enrollment: 169
Study Start Date: July 2007
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: D
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
Biological: cetuximab Drug: capecitabine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Other: immunohistochemistry staining method Other: laboratory biomarker analysis
Experimental: E
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
Biological: cetuximab Drug: capecitabine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Other: immunohistochemistry staining method Other: laboratory biomarker analysis

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640081

Locations
Cyprus
Bank of Cyprus Oncology Centre
Nicosia, Cyprus
United Kingdom
Bradford Royal Infirmary
Bradford, England, United Kingdom, BD9 6RJ
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Essex County Hospital
Colchester, England, United Kingdom, C03 3NB
Dorset County Hospital
Dorchester, England, United Kingdom, DT1 2JY
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom, GU2 7XX
St. Mary's Hospital
London, England, United Kingdom, W2 1NY
Hammersmith Hospital
London, England, United Kingdom, W12 OHS
Churchill Hospital
Oxford, England, United Kingdom, OX3 7LJ
Peterborough Hospitals Trust
Peterborough, England, United Kingdom, PE3 6DA
University Hospital of North Staffordshire
Stoke-On-Trent, England, United Kingdom, ST4 7LN
Singleton Hospital
Swansea, Wales, United Kingdom, SA2 8QA
Royal United Hospital
Bath, United Kingdom
Royal Bournemouth Hospital
Bournemouth, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
Darent Valley Hospital
Dartford, United Kingdom
Hereford County Hospital
Hereford, United Kingdom
Charing Cross Hospital
London, United Kingdom
Guys and St Thomas' hospitals
London, United Kingdom
Dorset Cancer Centre, Poole Hospital
Poole, United Kingdom
Weston Park
Sheffield, United Kingdom, S10 2SJ
Southport and Ormskirk
Southport, United Kingdom
St Helens and Whiston hospitals
St Helens, United Kingdom
Warrington and Halton Hospitals
Warrington, United Kingdom
Worcestershire Royal Hospital
Worcester, United Kingdom
Sponsors and Collaborators
Cheryl Pugh
Investigators
Principal Investigator: Harpreet S. Wasan Hammersmith Hospital
  More Information

No publications provided

Responsible Party: Cheryl Pugh, Trial Manager, Medical Research Council
ClinicalTrials.gov Identifier: NCT00640081     History of Changes
Other Study ID Numbers: CDR0000589635, MRC-CTU-COIN-B/CR11, EUDRACT:2006-003049-17, ISRCTN38375681, EU-20828, MERCK-MRC-CTU-COIN-B/CR11
Study First Received: March 19, 2008
Last Updated: February 23, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Cyprus: National Bioethics Committee of Cyprus

Keywords provided by Medical Research Council:
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

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Cetuximab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 26, 2014