- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01093092
Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery
A Phase I Clinical Trial of Oral Calcitriol With Fixed Dose of Cisplatin and Gemcitabine in Patients With Advanced Solid Tumors
Aperçu de l'étude
Statut
Les conditions
Description détaillée
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of oral calcitriol when combined with a standard dose of gemcitabine (gemcitabine hydrochloride) and cisplatin in a 28-day cycle.
SECONDARY OBJECTIVES:
I. Describe the toxicity of this combination using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
II. Study the pharmacokinetics of calcitriol at the maximum tolerated dose (MTD) in an expanded cohort of 6 patients.
III. Describe the clinical activity associated with this regimen in this advanced solid tumor population.
OUTLINE:
Patients receive calcitriol orally (PO) on days 1, 2, 8, 9, 15 and 16; cisplatin intravenously (IV) over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
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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Buffalo, New York, États-Unis, 14263
- Roswell Park Cancer Institute
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Virginia
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Charlottesville, Virginia, États-Unis, 22903
- Emily Couric Clinical 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:
- Patients with a diagnosis of advanced unresectable non-hematological malignancy that has no known standard of care or for which the use of gemcitabine plus cisplatin constitutes a reasonable option
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- White blood cell (WBC) >= 3.0 x 10^9/L
- Neutrophils >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Hemoglobin (Hgb) >= 10 g/dL
- Bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x institutional ULN unless metastatic to liver in which case AST and ALT should be < 5 x institutional ULN
- Creatinine =< 1.5 x institutional ULN
- Corrected calcium =< institutional ULN (corrected calcium = (4- Albumin) x 0.8 + calcium)
- Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
- Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- No treatment with investigational agents within 4 weeks prior to study drug administration, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
- No chemotherapy within 4 weeks prior to study treatment administration; nitrosoureas and mitomycin C are not allowed within 6 weeks prior to initiation of study treatment
- Palliative radiation, including whole brain radiation therapy (WBRT), is allowed prior to enrollment as long as it is completed > 2 weeks from initiation of study treatment, and provided patient has recovered from treatment toxicities to =< grade 1
- Patients should be able to take oral medications
Exclusion Criteria:
- Known hypersensitivity to any of the study drugs involved
- Brain metastases are excluded unless treated and shown to be controlled more than 1 month from after craniotomy or more than 2 weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
- History of clinically significant hypercalcemia
- Evidence of nephrectomy
- History of (within 24 months prior to enrollment) of kidney, ureter, or bladder stones with clinically significant sequelae (e.g. (painless gross hematuria; pain with or without infection; hydronephrosis, etc); patients with otherwise stable non-occluding kidney stones regardless of stone type incidentally found in computed tomography (CT) scans are eligible; patients with prior history of uric acid stones are eligible regardless of time of onset
- Unwillingness to stop calcium supplementation (during the first cycle of treatment) or vitamin D supplementation throughout the study
- Thiazide (e.g HCTZ, Hydrochoirthiazide) or digoxin therapy (e.g Lanoxicaps, Lanoxin)
- Pregnant or nursing female patients.
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug
- Received an investigational agent within 4 weeks prior to enrollment, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
- Nut allergy
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 |
|---|---|
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Expérimental: Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)
Patients receive calcitriol PO on days 1, 2, 8, 9, 15 and 16; cisplatin IV over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Études corrélatives
Autres noms:
Étant donné IV
Étant donné IV
Autres noms:
Bon de commande donné
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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MTD of oral calcitriol when combined with a standard dose of gemcitabine hydrochloride and cisplatin, determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0
Délai: 28 days
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A standard 3+3 with de-escalation will be used to estimate the MTD.
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28 days
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Toxicity of this combination, graded according to NCI CTCAE version 4.0
Délai: Up to 30 days after last dose of study drug
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Tabulated overall or by dose level (as appropriate).
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Up to 30 days after last dose of study drug
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Pharmacokinetic (PK) analyses of calcitriol at the MTD in an expanded cohort of 6 patients, including peak levels, area under the concentration-time curve from time 0-72 hours, terminal half-life, volume of distribution, and total body clearance
Délai: Days 1-3 of course 1
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PK data will be presented as plots of serum calcitriol concentration over time for each patient.
An assessment of whether systemic calcitriol exposure associated with antitumor activity in preclinical models is achieved in these patients will be made.
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Days 1-3 of course 1
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Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1
Délai: Up to 5 years
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Responses tabulated as appropriate.
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Up to 5 years
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Grace Dy, Roswell Park Cancer Institute
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
- 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
- Micronutriments
- Modulateurs de transport membranaire
- Vitamines
- Agents de conservation de la densité osseuse
- Hormones et agents régulateurs du calcium
- Agents vasoconstricteurs
- Agonistes des canaux calciques
- Gemcitabine
- Calcitriol
- Dihydroxycholécalciférols
Autres numéros d'identification d'étude
- I 163509 (Autre identifiant: Roswell Park Cancer Institute)
- P30CA016056 (Subvention/contrat des NIH des États-Unis)
- NCI-2010-00263 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
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