Clinical trial NCT00559741: Cetuximab and Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer
Official title: Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
recurrent colon cancer
stage IV rectal cancer
recurrent rectal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-11-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Improvement of hematologic and gastrointestinal tolerance to therapy
Secondary outcomes:
measure: Efficacy
measure: Genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of therapy
measure: Time to progression
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
Study officials:
affiliation: Institut Cancerologie de l'Ouest
name: Erick Gamelin, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.