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

NCT00640081 | Completed Phase 2 DMC

• 6 other identifiers: CDR0000589635MRC-CTU-COIN-B/CR11EUDRACT:2006-003049-17ISRCTN38375681EU-20828MERCK-MRC-CTU-COIN-B/CR11
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 25

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Failure-free survival at 10 months

  10 months

Secondary Outcomes (6)

• Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions

  12, 24 and 36 weeks

• Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks

  24 weeks

• Overall survival

  at 12, 24 and 36 weeks

• Progression-free survival

  at 12, 24 and 36 weeks

• Response rates

  at 12, 24 and 36 weeks

Study Arms (2)

D

ACTIVE COMPARATOR

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

E

EXPERIMENTAL

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

Interventions

cetuximab BIOLOGICAL

D; E

capecitabine DRUG

D; E

fluorouracil DRUG

D; E

leucovorin calcium DRUG

D; E

oxaliplatin DRUG

D; E

immunohistochemistry staining method OTHER

D; E

laboratory biomarker analysis OTHER

D; E

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Cheryl Pugh: lead

Study Sites (25)

Bank of Cyprus Oncology Centre

Nicosia, Cyprus

Location

Bradford Royal Infirmary

Bradford, England, BD9 6RJ, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Essex County Hospital

Colchester, England, C03 3NB, United Kingdom

Location

Dorset County Hospital

Dorchester, England, DT1 2JY, United Kingdom

Location

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, GU2 7XX, United Kingdom

Location

Hammersmith Hospital

London, England, W12 OHS, United Kingdom

Location

St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

Churchill Hospital

Oxford, England, OX3 7LJ, United Kingdom

Location

Peterborough Hospitals Trust

Peterborough, England, PE3 6DA, United Kingdom

Location

University Hospital of North Staffordshire

Stoke-on-Trent, England, ST4 7LN, United Kingdom

Location

Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

Location

Royal United Hospital

Bath, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

Darent Valley Hospital

Dartford, United Kingdom

Location

Hereford County Hospital

Hereford, United Kingdom

Location

Charing Cross Hospital

London, United Kingdom

Location

Guys and St Thomas' hospitals

London, United Kingdom

Location

Dorset Cancer Centre, Poole Hospital

Poole, United Kingdom

Location

Weston Park

Sheffield, S10 2SJ, United Kingdom

Location

Southport and Ormskirk

Southport, United Kingdom

Location

St Helens and Whiston hospitals

St Helens, United Kingdom

Location

Warrington and Halton Hospitals

Warrington, United Kingdom

Location

Worcestershire Royal Hospital

Worcester, United Kingdom

Location

Related Links

• Trial Summary on Sponsor's Website with trial citations

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Cetuximab; Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin; Immunohistochemistry

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Study Officials

• Harpreet S. Wasan

  Hammersmith Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Project manager for COINB for Sponsor

Study Record Dates

• First Submitted: March 19, 2008
• First Posted: March 20, 2008
• Study Start: July 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: September 1, 2015
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

CY (1); GB (24)