- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02573220
Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer
A UGT1A1 Genotype-Guided Dosing Study of Irinotecan Administered in Combination With 5-Fluorouracil/Leucovorin (FOLFIRI) and Cetuximab as First-Line Therapy in RAS Wild-Type Metastatic Colorectal Cancer Patients
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
PRIMARY OBJECTIVES:
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.
Type d'étude
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
-
-
-
Aviano, Italie, 33081
- Centro di Riferimento Oncologico
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of mCRC
- 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 both variant alleles (*28/*28)
- 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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: 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.
|
Étant donné IV
Autres noms:
Étant donné IV
Autres noms:
Étant donné IV
Autres noms:
Étant donné IV
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Maximum Tolerated Dose (MTD)
Délai: 28 days
|
The MTD recommended for phase II studies will be defined as the dose level immediately below the one at which 1 out of 3 patients or 1 out of 6 patients experienced DLT.
Therefore at the MTD, 1/3 out of at least 10 patients experienced DLT.
No intra-patient dose escalation is allowed.
There will be two genotype cohorts of patients: one for each genotype.
The cumulative hematological and non-hematological toxicities as well as the number of dose reductions and a delay in starting the next cycle of treatment will be used as secondary indicators to differentiate the two genotype cohorts of patients.
Patients can continue receiving the same dose of irinotecan in the absence of major toxicity if before retreatment they fully recover from any non-hematological toxicity, absolute neutrophil count is 1500 microliters and platelet count is 100,000 microliters.
Chemotherapy is discontinued on evidence of disease progression by RECIST version 1.1.
|
28 days
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Response rate
Délai: Every 2 cycles (every 8 weeks), from the beginning of the study until disease progression or death, which ever comes first (up to on average 60 months)
|
Response rate is the number of patients with a partial response (by RECIST version 1.1) divided by the total number of patients.
|
Every 2 cycles (every 8 weeks), from the beginning of the study until disease progression or death, which ever comes first (up to on average 60 months)
|
Progression-free survival (PFS)
Délai: From beginning of the study until disease progression or death, which every comes first (up to on average 60 months)
|
PFS is the time (in days) between study enrollment and disease progression (by RECIST version 1.1) or death, whichever comes first.
|
From beginning of the study until disease progression or death, which every comes first (up to on average 60 months)
|
metastectomy (with curative intent) rate
Délai: Within 1 year of starting therapy
|
Metastatectomy rate is the number of patients who undergo a surgical resection with curative intent divided by the total number of patients
|
Within 1 year of starting therapy
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Manish Sharma, University of Chicago Comprehensive Cancer Center
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Tumeurs
- Tumeurs par site
- Tumeurs gastro-intestinales
- Tumeurs du système digestif
- Maladies gastro-intestinales
- Maladies du côlon
- Maladies intestinales
- Tumeurs intestinales
- Maladies rectales
- Tumeurs colorectales
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents protecteurs
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase
- Agents antinéoplasiques immunologiques
- Micronutriments
- Vitamines
- Hormones et agents régulateurs du calcium
- Inhibiteurs de la topoisomérase I
- Antidotes
- Complexe de vitamine B
- Fluorouracile
- Leucovorine
- Irinotécan
- Calcium
- Lévoleucovorine
- Cétuximab
- Camptothécine
Autres numéros d'identification d'étude
- IRB15-0081 (Autre identifiant: University of Chicago Comprehensive Cancer Center)
- P30CA014599 (Subvention/contrat des NIH des États-Unis)
- NCI-2015-01432 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Cancer colorectal de stade IVA
-
University of Southern CaliforniaNational Cancer Institute (NCI); Prism Pharma Co., Ltd.RetiréAdénocarcinome colorectal | Cancer colorectal de stade IVA | Cancer colorectal de stade IVBÉtats-Unis
-
University of Wisconsin, MadisonMerck Sharp & Dohme LLCComplétéCancer colorectal | Adénocarcinome colorectal | Cancer colorectal de stade IVA | Cancer colorectal de stade IVB | Carcinome métastatique dans le foieÉtats-Unis
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLCComplétéCarcinome colorectal récurrent | Cancer colorectal de stade IVA | Cancer colorectal de stade IVBÉtats-Unis
-
City of Hope Medical CenterNational Cancer Institute (NCI)RésiliéCarcinome colorectal récurrent | Cancer colorectal de stade IVA | Cancer colorectal de stade IVBÉtats-Unis
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Actif, ne recrute pasCarcinome colorectal métastatique | Cancer colorectal de stade IV AJCC v8 | Cancer colorectal de stade IVA AJCC v8 | Cancer colorectal de stade IVB AJCC v8 | Cancer colorectal de stade IVC AJCC v8États-Unis
-
M.D. Anderson Cancer CenterActif, ne recrute pasCancer colorectal de stade IV | Cancer colorectal de stade IVA | Cancer colorectal de stade IVB | Type sauvage RASÉtats-Unis
-
Emory UniversityBristol-Myers Squibb; National Cancer Institute (NCI); National Institutes of...Actif, ne recrute pasCancer colorectal métastatique | Adénocarcinome colorectal | Cancer colorectal de stade IV | Cancer colorectal de stade IVA | Cancer colorectal de stade IVB | Carcinome colorectal réfractaire | Carcinome colorectal stable microsatellite métastatique | Cancer colorectal de stade IVCÉtats-Unis
-
University of Southern CaliforniaNational Cancer Institute (NCI)RésiliéCancer colorectal de stade IV | Cancer colorectal de stade IVA | Cancer colorectal de stade IVB | Carcinome métastatiqueÉtats-Unis
-
Ning JinActif, ne recrute pasCarcinome colorectal métastatique | Cancer colorectal de stade IV AJCC v8 | Cancer colorectal de stade IVA AJCC v8 | Cancer colorectal de stade IVB AJCC v8 | Cancer colorectal de stade IVC AJCC v8États-Unis
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)ComplétéCancer colorectal de stade IV AJCC v7 | Cancer colorectal de stade IVA AJCC v7 | Cancer colorectal de stade IVB AJCC v7 | Adénocarcinome colorectal | Type sauvage RASÉtats-Unis
Essais cliniques sur Fluorouracile
-
Hong Kong Nasopharyngeal Cancer Study Group LimitedThe Hong Kong Anti-Cancer Society; hong Kong Cancer FundComplété
-
Associazione Volontari Pazienti OncologiciMario Negri Institute for Pharmacological ResearchComplétéCarcinome épidermoïde de la tête et du couItalie
-
TG Therapeutics, Inc.SCRI Development Innovations, LLCComplétéCancer de l'estomac | Cancer colorectal | Cancer du pancréas | Cancer de l'oesophage | Cancer rectal | Tumeur stromale gastro-intestinale (GIST)États-Unis
-
CStone PharmaceuticalsActif, ne recrute pasCarcinome épidermoïde de l'œsophage localement avancé, récurrent ou métastatique non résécableChine
-
Actavis Inc.Complété
-
Fundación Pública Andaluza para la gestión de la...Complété
-
Dr. Gordon BuduhanUniversity of Toronto; London Health Sciences Centre; CancerCare ManitobaRecrutementCancer de l'oesophage | Adénocarcinome œsophagien | Adénocarcinome, jonction gastro-oesophagienneCanada
-
mAbxience Research S.L.Laboratorio Elea Phoenix S.A.; Libbs Farmacêutica LTDAComplétéCancer colorectal métastatique (mCRC)Argentine, Brésil, Inde, Espagne, Ukraine
-
ClinAssessSanofi; Merck Sharp & Dohme LLCComplétéCarcinome épidermoïde de l'hypopharynx | Carcinome du larynxAllemagne, L'Autriche
-
National Cancer Institute (NCI)Actif, ne recrute pasNéoplasie cervicale intraépithéliale Grade 2/3 | Néoplasie intraépithéliale cervicale de haut grade | Carcinome épidermoïde cervical in situ | Néoplasie intraépithéliale malpighienne cervicale 2États-Unis