Cetuximab and Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer

NCT ID: NCT00559741

Last Updated: 2011-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31

Brief Summary

RATIONALE: 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. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works in treating patients with advanced or metastatic colorectal cancer.

Detailed Description

OBJECTIVES:

Primary

• Improve hematologic and gastrointestinal tolerance to cetuximab and irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with advanced or metastatic colorectal cancer.

Secondary

• Increase the effectiveness of this regimen by intensifying the treatment.
• Specify the constitutional genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of this regimen.
• Assess the time to progression.

OUTLINE: This is a multicenter study.

Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and cetuximab IV over 1-2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Pharmacokinetic and pharmacogenetic studies are also conducted.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cetuximab

Intervention Type: BIOLOGICAL

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Advanced or metastatic disease
• Scheduled to receive first- or second-line therapy for metastatic disease
• No cerebral metastases or symptomatic or uncontrolled meningeal disease

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• ANC ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No intestinal blockage
• No complete dihydropyrimidine dehydrogenase deficiency
• No chronic inflammatory disease of the colon
• No other cancer except for nonmelanoma skin cancer or curatively treated carcinoma of the cervix or breast
• No other severe condition, or condition that is likely to worsen, including any of the following:

• Unstable heart disease
• Myocardial infarction within the past 6 months
• Active uncontrolled infection
• No contraindication to atropine

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior anticancer therapy
• More than 4 weeks since prior and no other concurrent investigational therapy
• Prior adjuvant chemotherapy allowed
• No prior fluorouracil or irinotecan hydrochloride
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Cancerologie de l'Ouest

OTHER

Sponsor Role: lead

Principal Investigators

Erick Gamelin, MD

Role: STUDY_CHAIR

Institut Cancerologie de l'Ouest

Locations

Centre Paul Papin

Angers, , France

Countries

France

References

Rouits E, Charasson V, Petain A, Boisdron-Celle M, Delord JP, Fonck M, Laurand A, Poirier AL, Morel A, Chatelut E, Robert J, Gamelin E. Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Br J Cancer. 2008 Oct 21;99(8):1239-45. doi: 10.1038/sj.bjc.6604673. Epub 2008 Sep 16.

Reference Type: RESULT

PMID: 18797458 (View on PubMed)

Lobet S, Paintaud G, Azzopardi N, Passot C, Caulet M, Chautard R, Desvignes C, Capitain O, Tougeron D, Lecomte T, Ternant D. Relationship Between Cetuximab Target-Mediated Pharmacokinetics and Progression-Free Survival in Metastatic Colorectal Cancer Patients. Clin Pharmacokinet. 2023 Sep;62(9):1263-1274. doi: 10.1007/s40262-023-01270-2. Epub 2023 Jul 13.

Reference Type: DERIVED

PMID: 37442917 (View on PubMed)

Rollin J, Payance A, Gouilleux-Gruart V, Boisdron-Celle M, Azzopardi N, Morel A, Gruel Y, Paintaud G, Gamelin E, Watier H, Lecomte T. Significant effect of VEGFA polymorphisms on the clinical outcome of metastatic colorectal cancer patients treated with FOLFIRI-cetuximab. Pharmacogenomics. 2015 Dec;16(18):2035-43. doi: 10.2217/pgs.15.139. Epub 2015 Nov 30.

Reference Type: DERIVED

PMID: 26615857 (View on PubMed)

Other Identifiers

CPP-FOLFIRICETUX

Identifier Type: -

Identifier Source: secondary_id

INCA-RECF0108

Identifier Type: -

Identifier Source: secondary_id

CDR0000574065

Identifier Type: -

Identifier Source: org_study_id