- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00376727
Cetuximab in Treating Patients With Advanced Solid Tumors
A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors
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.
PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab in treating patients with advanced solid tumors.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of cetuximab in patients with advanced solid tumors.
Secondary
- Evaluate the safety and tolerability of this drug in these patients.
- Develop a detailed scale for assessment of rash in these patients.
- Investigate potential predictors of response using correlative studies on patient tissue, buccal mucosa, and blood samples.
- Obtain preliminary efficacy data and evaluate the relationship of efficacy to grade of rash.
- Correlate downstream markers (e.g., pMAPK, pAKT, and Ki-67) and the presence of epidermal growth factor receptor (EGFR) polymorphisms with clinical response and/or survival.
- Examine the levels of downstream marker proteins in buccal cells obtained pre- and post-treatment.
- Correlate basal p27 expression levels with response and/or survival.
- Determine if the presence of a K-RAS mutation influences response or survival outcome.
- Correlate the presence or absence of mutant K-RAS tumor DNA shed into patient plasma with response and/or outcome.
- Correlate levels of cytokines and chemokines with rash and clinical response.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive cetuximab IV over 90 minutes once weekly for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and buccal mucosa collection at baseline and prior to courses 2 and 3 of treatment for molecular correlative studies. Archival tumor tissue specimens are also used for molecular correlative studies. Immunologic correlative studies are performed using patient blood samples.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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California
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Sacramento, California, États-Unis, 95817
- University of California Davis Cancer Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Signed written informed consent
- Histologically or cytologically proven advanced solid tumors not curable by surgery, radiation therapy or standard chemo-, immuno-, or hormonal therapy. A specific primary cancer need not have been identified (i.e., unknown primary is eligible).
- Patients must have received at least one prior regimen (chemotherapy and/or radiation) for metastatic disease. There is no limit to the number of prior therapies.
- Any prior chemotherapy must have been completed at least 4 weeks prior to start of study therapy. Previous radiation therapy must have been completed at least 2 weeks prior to start of study therapy. All side effects of prior therapy must be resolved prior to the start of study therapy.
- Patients with ZUBROD performance status 0-2 (see Appendix 1).
- Patients must have measurable disease or evaluable disease.
- Patients must have an estimated survival of at least 3 months.
- Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids for at least 4 weeks.
- Patients >/= 18 years of age.
- Patients of reproductive potential must agree to use an effective contraceptive method while on treatment and for 3 months afterward as the effects of cetuximab on the unborn fetus are unknown.
- Patients must have adequate hematologic function defined as: ANC >/= 1,500/mm3, platelets >/= 100,000/mm3.
- Patients must have adequate hepatic function defined as SGOT </= 3 x institutional UNL and serum bilirubin </= 2.0 mg/dL.
- Patients must have adequate renal function defined as a serum creatinine level </= 1.6 mg/dL or a calculated creatinine clearance of >/= 40 ml/min.
Exclusion Criteria:
- Female patients cannot be pregnant or breastfeeding as the effects of cetuximab on the unborn fetus are unknown. Documentation of a negative pregnancy test prior to treatment is required for all women of reproductive potential.
- Uncontrolled intercurrent illness including but not limited to ongoing infection or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Patients with symptomatic brain metastasis or still requiring steroids.
- Patients who have received prior cetuximab therapy, prior therapy with any other drug that targets the EGF receptor (including, but not limited to, Iressa, Tarceva, Herceptin, CI1033, etc.), or prior therapy with a monoclonal antibody.
- Patients who have received prior chemotherapy within 4 weeks or radiation therapy within 2 weeks prior to the start of study therapy.
- Prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy.
- Patients may not receive any other chemotherapy, radiation therapy, or biologic therapy while on study.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Phase I dose escalation study
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Dose level 0: cetuximab 400 mg/m2 week 1, 250 mg/m2 weekly; Dose level 1: cetuximab 400 mg/m2 week 1, 300 mg/m2 weekly; Dose level 2: cetuximab 400 mg/m2 week 1, 350 mg/m2 weekly; Dose level 3: cetuximab 400 mg/m2 week 1, 400 mg/m2 weekly
Autres noms:
Tissue and Blood Specimens; IHC Methodology; IHC Scoring; K-RAS Mutation Analysis
Peripheral Blood Mononuclear Cells (PBMC)
Cetuximab Pharmacodynamics
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
---|---|
Maximum tolerated dose of cetuximab
Délai: December 2007
|
December 2007
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
---|---|
Safety and tolerability of cetuximab
Délai: December 2007
|
December 2007
|
Potential predictors of response using correlative studies
Délai: December 2007
|
December 2007
|
Correlation of efficacy of cetuximab with grade of skin rash
Délai: December 2007
|
December 2007
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Development of a detailed scale for assessing skin rash
Délai: December 2007
|
December 2007
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Angela Davies, MD, University of California, Davis
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
Autres numéros d'identification d'étude
- CDR0000506089
- P30CA093373 (Subvention/contrat des NIH des États-Unis)
- UCDCC-165 (Autre identifiant: University of California, Davis - Cancer Center)
- BMS-CA225027 (Autre subvention/numéro de financement: Bristol-Myers Squibb)
- 200412499 (Autre identifiant: University of California, Davis - IRB)
- IMCL-8420 (Autre subvention/numéro de financement: Imclone Systems, Inc.)
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 .
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