- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00243100
Vorinostat and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors
A Phase 1 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Gemcitabine in Patients With Epithelial Tumors
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity, maximum tolerated dose, and pharmacokinetics of vorinostat (SAHA) and gemcitabine in patients with metastatic or unresectable epithelial solid tumors.
SECONDARY OBJECTIVES:
II. Determine tumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation, open-label study.
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine 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. A minimum of 6 patients are treated at the MTD.
After completion of study treatment, patients are followed for 30 days.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
-
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Texas
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Houston, Texas, États-Unis, 77030
- M D Anderson 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:
- ECOG 0-2 OR Karnofsky 60-100%
- AST and ALT =< 2.5 times ULN
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- Platelet count >= 100,000/mm3
- Absolute neutrophil count >= 1,500/mm3
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Any number and type of prior chemotherapies are allowed including prior use of gemcitabine chemotherapy. A washout phase of at least 2 weeks since use of prior chemotherapy or radiation therapy, 6 weeks if the last regimen included nitrosoureas or mitomycin C, is required.
- Patients must have histologically confirmed epithelial malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients must have at least one measurable lesion as per the RECIST Criteria that can be accurately measured in at least one dimension, with minimum lesion size equal to or more than twice the slice thickness of the imaging study used.
Exclusion Criteria:
- No symptomatic congestive heart failure
- No cardiac arrhythmia
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No history of allergy, significant side effects, or poor tolerance to gemcitabine
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to vorinostat (SAHA)
- At least 2 weeks since prior radiotherapy
- Recovered from prior therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other uncontrolled illness
- More than 2 weeks since prior valproic acid
- No other concurrent investigational drugs
- No other concurrent anticancer therapy
- Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
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: Arm I
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and gemcitabine IV over 1-2 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA and gemcitabine 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. A minimum of 6 patients are treated at the MTD |
Étant donné IV
Autres noms:
Donné oralement
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
---|---|
Maximally tolerated dose of a combination of SAHA and gemcitabine determined by dose-limiting toxicity as measured by NCI CTCAE v3.0 continuously
Délai: 21 days
|
21 days
|
Pharmacokinetics of SAHA
Délai: -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours after day 1 dose; -0.5 hours day 2; and -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours day 3
|
-0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours after day 1 dose; -0.5 hours day 2; and -0.5, 0.5, 1, 2, 2.5, 3, 4, 6 and 8 hours day 3
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
---|---|
Best overall response (complete + partial response rate) as measured radiologically by RECIST
Délai: Up to 6 years
|
Up to 6 years
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Gauri Varadhachary, M.D. Anderson 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
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Inhibiteurs de l'histone désacétylase
- Gemcitabine
- Vorinostat
Autres numéros d'identification d'étude
- NCI-2009-00091 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- U01CA062461 (Subvention/contrat des NIH des États-Unis)
- CDR0000445401
- 2005-0140 (Autre identifiant: M D Anderson Cancer Center)
- 6865 (Autre identifiant: CTEP)
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