Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer
NCT ID: NCT02573220
Last Updated: 2016-12-09
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE1
INTERVENTIONAL
2015-06-30
2016-08-31
Brief Summary
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Detailed Description
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I. To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the phase II recommended dosage of irinotecan (irinotecan hydrochloride) administered in the FOLFIRI regimen plus cetuximab in metastatic colorectal cancer (mCRC) patients with \*1/\*1 and \*1/\*28 uridine diphosphate glucuronosyltransferase (UGT1A1) genotype treated as first line chemotherapy.
SECONDARY OBJECTIVE:
To estimate the response rate, progression-free survival (PFS) and metastasectomy (with curative intent) rate in the overall patient population (both genotype cohorts).
OTHER OBJECTIVES:
I. To evaluate the variability of irinotecan pharmacokinetics, in combination with cetuximab, in patients with \*1/\*1 and \*1/\*28 genotype and the effect of the pharmacokinetic profile on toxicity and response rate.
II. To evaluate the pharmacokinetic profile of irinotecan and its major metabolites in the absence and the presence of cetuximab administration, in order to define the effect of the chimeric monoclonal antibody on irinotecan pharmacokinetics.
OUTLINE: This is a dose-escalation study of irinotecan hydrochloride in patients with UGT1A1.
Patients receive irinotecan hydrochloride intravenously (IV) over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (FOLFIRI and cetuximab)
Patients receive irinotecan hydrochloride IV over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cetuximab
Given IV
Fluorouracil
Given IV
Irinotecan Hydrochloride
Given IV
Leucovorin Calcium
Given IV
Interventions
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Cetuximab
Given IV
Fluorouracil
Given IV
Irinotecan Hydrochloride
Given IV
Leucovorin Calcium
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* RAS wild-type status (by a Clinical Laboratory Improvement Amendments \[CLIA\] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog \[KRAS\], Harvey rat sarcoma viral oncogene homolog \[HRAS\], and neuroblastoma RAS viral (v-ras) oncogene homolog \[NRAS\])
* No prior chemotherapy for metastatic disease
* Able to understand and provide written informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy \> 3 months
* Measurable or evaluable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria, i.e. lesions that can be accurately measured in at least one dimension with the longest diameter \>= 20 mm using conventional techniques or \>= 10 mm using spiral computed tomography (CT) scan
* Absolute neutrophil count (ANC) \> l500/ul
* Hemoglobin \> 9g/dL
* Platelets \> 100,000/ul
* Total bilirubin =\< 1.5 times upper limit of normal
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times upper limit of normal
* Alkaline phosphatase \< 2.5 times the upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Creatinine \< 1.5 mg/dL
* Patients genotyped for UGT1A1\*28 polymorphism with \*1/\*1 or \*1/\*28 genotype
* Men and women of childbearing potential must agree to use adequate contraception (double barrier birth control) for the duration of study therapy
* Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential
Exclusion Criteria
* Patients with any polymorphism in UGT1A1 other than \*1 or \*28 (e.g, \*6)
* Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis
* Patients with specific contraindications to the use of anti-EGFR therapy such as pulmonary fibrosis, interstitial pneumonia history
* Unresolved diarrhea and bowel obstruction
* Active bleeding
* Documented cerebral metastasis
* Serious active infectious disease
* Pregnancy
* Radiotherapy or major surgery within 4 weeks
* Psychiatric illness or social situations that would limit compliance with study requirements
* Presence of previous or concomitant neoplasm with exclusion of in situ cervical cancer
* Patients taking substrates, inhibitors and inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
University of Chicago
OTHER
Responsible Party
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Principal Investigators
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Manish Sharma
Role: PRINCIPAL_INVESTIGATOR
University of Chicago Comprehensive Cancer Center
Locations
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Centro di Riferimento Oncologico
Aviano, , Italy
Countries
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Other Identifiers
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NCI-2015-01432
Identifier Type: REGISTRY
Identifier Source: secondary_id
IRB15-0081
Identifier Type: OTHER
Identifier Source: secondary_id
IRB15-0081
Identifier Type: -
Identifier Source: org_study_id