3-AP in Treating Patients With Advanced or Metastatic Solid Tumors
A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors.
II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients.
III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess tumoral expression of genes involved in response and resistance to 3-AP.
V. Observe and record any tumor response in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral 3-AP 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. Blood samples for pharmacokinetic analysis are collected periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP during course 1.
After completion of study treatment, patients are followed periodically.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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California
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Duarte, California, États-Unis, 91010
- City of Hope
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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
Criteria:
- Must be able to swallow
- Histologically confirmed solid tumor
- Advanced or metastatic disease
- Measurable or evaluable disease
- No known active CNS metastases
- ECOG performance status 0-1
- Life expectancy > 3 months
- Progressive disease during >= 1 prior standard therapy OR disease unlikely to respond to any currently available therapies
- Patients with previously treated CNS metastases who have no evidence of new CNS metastases AND are stable for >= 2 months are eligible
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 10 g/dL (transfusions allowed)
- Absolute neutrophil count >= 1,500/mm^3
- ALT and AST =< 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase =< 2.5 times ULN
- Creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min
- Bilirubin normal
- PT/PTT =< 1.5 times ULN
- FEV1 >= 1.2 L
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception 2 weeks prior to and during study treatment
- No mental deficits and/or psychiatric history that may preclude study treatment
- No active heart disease, including any of the following: myocardial infarction within the past 3 months, symptomatic coronary artery disease or heart block, uncontrolled congestive heart failure
- No moderate to severe compromise of pulmonary function
- No active infection
- No other life-threatening illness
- No active coagulation disorder other than occult blood
- No known positivity for glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Recovered from prior treatment
- Prior gemcitabine allowed
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 3 weeks since prior radiotherapy or any other treatment for this cancer
- No prior 3-AP
- No concurrent radiotherapy
- No other concurrent investigational agent
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 will receive a 2-hour infusion of 3-AP once in week 1.
Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks.
Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown.
|
Given IV and orally
Autres noms:
étude corrélative
Autres noms:
Étude corrélative
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0
Délai: 28 days
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28 days
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Serum pharmacokinetics of oral triapine
Délai: Baseline, day 4, and day 8
|
Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate.
The relationship of the AUC to the dose will be assessed by least-square regression analysis.
|
Baseline, day 4, and day 8
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Yun Yen, City of Hope Medical 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
Autres numéros d'identification d'étude
- NCI-2009-00139 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- U01CA062505 (Subvention/contrat des NIH des États-Unis)
- PHI-52 (Autre identifiant: City of Hope)
- CDR0000507731
- 7225 (Autre identifiant: CTEP)
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