A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)
27 février 2019 mis à jour par: Merck Sharp & Dohme LLC
A Phase I Study of Ridaforolimus in Pediatric Patients With Advanced Solid Tumors
The main objectives of this trial are to determine the recommended dose of ridaforolimus for pediatric participants with advanced solid tumors by measuring the number of participants experiencing dose-limiting toxicities (DLTs) while on different doses of ridaforolimus, and to characterize the pharmacokinetics of ridaforolimus in these participants. The primary hypotheses of this study are that 1) the DLTs observed will be dose-dependent and allow for definition of a maximum tolerated dose (MTD) and 2) at a safe and well tolerated dose, ridaforolimus geometric mean (GM) Day-5 blood area under the concentration-time curve at 24 hours (AUC0-24) exceeds 75% (or 1304-ng*hr/mL) of the estimated GM Day-5, 40-mg AUC0-24 in adults.
Study-related visits concluded in August 2013. Participants who did not have disease progression, adequately tolerated therapy, and continued to meet eligibility criteria for 6 months after the enrollment period had been completed could continue treatment in an extension phase until they met discontinuation criteria or voluntarily withdrew.
Aperçu de l'étude
Type d'étude
Interventionnel
Inscription (Réel)
20
Phase
- La phase 1
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
6 ans à 17 ans (Enfant)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion criteria:
- Histologic or cytologic diagnosis of a malignant solid tumor, including tumors of the central nervous system and lymphoma, that have progressed despite standard therapy or for which no effective standard therapy is known. Participants who have received standard therapy and continue to have biopsy-proven residual stable disease are eligible
- Measurable or non-measurable disease
- Must be able to swallow tablets
- Performance Status: Lansky Play Scale ≥70 for children <10 years of age; Karnofsky score ≥70 for children ≥10 to <16 years; or Eastern Cooperative Oncology Group (ECOG) Status 0-2 for patients age 16 and older
- Adequate organ function
- For females of reproductive potential, a negative pregnancy test must be documented within 72 hours of receiving the first dose of study medication
- Participants of reproductive potential must agree to use (or have their partner use) adequate contraception throughout the study, starting with Visit 1 through 30 days after the last dose of study drug
Exclusion criteria:
- Currently receiving any other investigational agents or using any investigational devices
- Leukemia
- Participant previously received ridaforolimus, rapamycin, or other rapamycin analogs
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ridaforolimus
- Persistent acute toxicity from previous therapy ≥Grade 2 (excluding alopecia, neuropathy, or hearing loss)
- Uncontrolled intercurrent illness despite adequate therapy
- Pregnant or breastfeeding
- Requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A)
- Poorly controlled Type 1 or 2 diabetes
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Ridaforolimus 22 mg/m^2
Participants receive 22 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months.
Eligible participants can receive additional treatment in an extension phase of the study.
|
Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.
Autres noms:
|
|
Expérimental: Ridaforolimus 28 mg/m^2
Participants receive 28 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months.
Eligible participants can receive additional treatment in an extension phase of the study.
|
Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.
Autres noms:
|
|
Expérimental: Ridaforolimus 33 mg/m^2
Participants receive 33 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months.
Eligible participants can receive additional treatment in an extension phase of the study.
|
Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
Délai: Cycle 1 (cycle = 28 days)
|
DLT defined using NCI-CTCAE v.4.0 as any of the following events occurring during the first 28-day cycle that were possibly, probably, or definitely study drug-related: Grade 4 neutropenia for ≥5 days; Grade 3-4 neutropenia associated with fever, antibiotics, or hospitalization for infection; Grade 4 thrombocytopenia for ≥5 days or requiring platelet transfusion; ≥Grade 3 hyperglycemia for ≥5 days despite management; ≥Grade 3 diarrhea for >24 hours despite management; ≥Grade 3 nausea or vomiting despite management; any other Grade ≥3 non-hematological toxicity persisting despite management (except alopecia, transient electrolyte abnormalities, transient Grade 3 liver function test elevations, and Grade 3 neurotoxicity for participants with baseline Grade 3 neurotoxicity); inability to complete DLT assessment period, interruption in dosing for >10 dosing days during DLT assessment period, or any delay in the initiation of the next cycle for >10 dosing days due to any related toxicity.
|
Cycle 1 (cycle = 28 days)
|
|
Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)
Délai: Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus
|
AUC is a measure of the amount of drug in the blood over time.
Whole blood samples were collected pre-dose (within 5 minutes of ridaforolimus administration) and post-dose at specified time points on Day 5 of the first week of Cycle 1 to determine AUC0-24 hr.
|
Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
30 janvier 2012
Achèvement primaire (Réel)
20 août 2013
Achèvement de l'étude (Réel)
25 mai 2018
Dates d'inscription aux études
Première soumission
7 septembre 2011
Première soumission répondant aux critères de contrôle qualité
7 septembre 2011
Première publication (Estimation)
9 septembre 2011
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
1 mars 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
27 février 2019
Dernière vérification
1 février 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 8669-056
- 2011-000729-55 (Numéro EudraCT)
- MK-8669-056 (Autre identifiant: Merck Protocol Number)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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