- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00080990
Alvocidib, Oxaliplatin, Fluorouracil, and Leucovorin Calcium in Treating Patients With Advanced Solid Tumors
An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
I. Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
II. Determine the pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
IV. Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients.
V. Determine the safety and tolerability of this regimen in these patients. VI. Correlate p21, p53, and apoptotic markers with response in patients treated with this regimen.
OUTLINE: This is a non-randomized, open-label, dose-escalation study of flavopiridol.
Patients receive alvocidib intravenously (IV) over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of alvocidib 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. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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New York
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New York, New York, États-Unis, 10065
- Memorial Sloan-Kettering 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:
Histologically confirmed advanced solid tumor
- Refractory to standard therapy or no standard therapy exists
- Evaluable disease
No known untreated CNS metastases
- Patients who have undergone local treatment for brain metastases and whose brain metastases are stable by repeat imaging study performed ≤ 4 weeks after treatment are allowed
- No primary CNS tumors
- Performance status - Karnofsky 60-100%
- WBC ≥ 3,500/mm^3
- Neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)
- Creatinine ≤ 1.5 mg/dL
- No cardiac arrhythmias within the past 6 months
- No congestive heart failure within the past 6 months
- No myocardial infarction within the past 6 months
- No arterial or venous thrombosis within the past year
- No peripheral neuropathy > grade 1
- No other medical condition that would preclude study participation
- No serious or uncontrolled infection
- HIV negative
Not pregnant or nursing
- No nursing during and for 2 months after study participation
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study participation
- At least 2 weeks since prior immunotherapy
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
- No prior flavopiridol
- At least 2 weeks since prior radiotherapy
- Recovered from all prior therapy
No concurrent therapy for thrombosis
- Prophylaxis for central lines or deep vein thrombosis allowed
- No other concurrent investigational medications
No concurrent vitamins, antioxidants, or herbal preparations and supplements
- Concurrent single-tablet multivitamin allowed
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 (alvocidib with oxaliplatin, 5-FU, leucovorin)
Patients receive alvocidib IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol 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. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose. |
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 of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium
Délai: 6 weeks
|
Defined as the dose level immediately preceding the dose where 2 or more patients experienced dose-limiting toxicity.
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6 weeks
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
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Dose-limiting toxicity as defined by the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 3 treatments in 6 weeks
Délai: 6 weeks
|
6 weeks
|
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Recommended phase II dose of alvocidib
Délai: 6 weeks
|
6 weeks
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Gary Schwartz, Memorial Sloan Kettering Cancer Center
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (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
- Tumeurs
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents protecteurs
- Substances de croissance
- Inhibiteurs de croissance
- Micronutriments
- Inhibiteurs de protéine kinase
- Vitamines
- Hormones et agents régulateurs du calcium
- Antidotes
- Complexe de vitamine B
- Fluorouracile
- Oxaliplatine
- Leucovorine
- Calcium
- Lévoleucovorine
- Alvocidib
Autres numéros d'identification d'étude
- NCI-2009-00055 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- U01CA069856 (Subvention/contrat des NIH des États-Unis)
- MSKCC-03146
- CDR0000357606
- NCI-6365
- 03-146A (Autre identifiant: Memorial Sloan-Kettering Cancer Center)
- 6365 (Autre identifiant: CTEP)
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