- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00060632
Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)
A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Weekly Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
The primary objectives of the study are to determine the safety, tolerability, and MTD of ridaforolimus when administered once weekly for 4 weeks (4 week cycle). The secondary objectives of the study are to characterize the pharmacokinetic profile of ridaforolimus, to evaluate potential pharmacodynamic markers of ridaforolimus, and to obtain preliminary information on the antineoplastic activity of ridaforolimus.
Protocol Outline: This is a dose-escalation study. Patients receive ridaforolimus over 30 minutes by intravenous infusion once weekly for 8 weeks (two 4-week cycles). If tolerated, a total of at least 2 cycles will be administered (8-week treatment period). Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
(Patients must meet each of the following criteria to be eligible for participation in the study).
- Male or female patients, ≥ 18 years of age.
- Patients with a documented measurable or evaluable malignancy, including myeloma or lymphoma, that is recurrent, advanced, or metastatic.
- Patients with disease that is currently refractory to, or not amenable to, standard therapy.
- Patients with disease that is currently not amenable to surgical intervention.
- Patients with Karnofsky performance status of ≥ 70% (Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1) and an anticipated life expectancy of ≥ 3 months.
- Patients either not of childbearing potential, or agreeing to use a medically effective method of contraception.
- Patients with the ability to understand and give written informed consent.
Exclusion Criteria:
(Patients meeting any of the following criteria are ineligible for participation in the study)
- Women who are pregnant or lactating.
- Patients with primary central nervous system (CNS) malignancies. Patients with leukemia, any form.
- Patients with certain hematologic abnormalities.
- Patients with certain serum chemistry abnormalities at baseline.
- Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween 80) or any other excipient contained in the test drug formulation.
- Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).
- Patients with significant cardiovascular disease.
- Patients with active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy. Note: Patients with treated brain metastases will be eligible if they are on a stable dose of corticosteroids or are without change in brain disease status for at least 4 weeks following related therapy (e.g., whole brain radiation, surgery).
- Patients with known human immunodeficiency virus (HIV) infection.
- Patients with any active infection.
- Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 2 weeks prior to study entry. Note: Patients having undergone recent placement of a central venous access port will be considered eligible for enrollment if they have recovered.
- Patients who have any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the test drug.
- Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
- Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements.
Drugs and Other Treatments to be Excluded (Either during or within 4 weeks prior to study entry, unless otherwise noted)
- Chemotherapeutic agents (standard or experimental).
- Other antineoplastic agents.
- Immunotherapy (including vaccines) or biological response modifier therapy.
- Systemic replacement hormonal therapy for life-threatening non-oncology diseases.
- Herbal preparations or related over-the-counter (OTC) preparations containing herbal ingredients (e.g., St John's Wort) during or within 2 weeks prior to study entry.
- Any prior therapy with rapamycin, CCI-779, or any other rapamycin analog.
- Any other experimental therapy during the course of the study.
- Radiotherapy for the primary malignancy or metastases.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Cohort 1: Ridaforolimus 6.25 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Expérimental: Cohort 2: Ridaforolimus 12.5 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Expérimental: Cohort 3: Ridaforolimus 25 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Expérimental: Cohort 4: Ridaforolimus 50 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Expérimental: Cohort 5: Ridaforolimus 100 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Expérimental: Cohort 6: Ridaforolimus 75 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
---|---|
Maximum Tolerated Dose (MTD)
Délai: Cycle 1 (within the first 4 weeks)
|
Cycle 1 (within the first 4 weeks)
|
Number of Participants Reporting Adverse Events (AE)
Délai: Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
Number of Participants Discontinuing Due to AEs
Délai: Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
---|---|
Best Overall Tumor Response
Délai: 8 weeks
|
8 weeks
|
Maximum Concentration (Cmax) of Ridaforolimus
Délai: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Area Under the Curve (AUC[0 to Infinity]) of Ridaforolimus
Délai: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Apparent Terminal Half-Life (t1/2) of Ridaforolimus
Délai: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Clearance (CL) of Ridaforolimus
Délai: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Volume of Distribution at Steady State (Vss) of Ridaforolimus
Délai: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Phosphorylated 4E Binding Protein 1 (Phospho-4E-BP1) Blood Levels
Délai: Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Publications et liens utiles
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
- Maladies cardiovasculaires
- Maladies vasculaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Maladies hématologiques
- Troubles hémorragiques
- Troubles hémostatiques
- Paraprotéinémies
- Troubles des protéines sanguines
- Tumeurs, plasmocyte
- Myélome multiple
- Effets physiologiques des médicaments
- Agents anti-infectieux
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antibactériens
- Antibiotiques, Antinéoplasiques
- Agents antifongiques
- Sirolimus
Autres numéros d'identification d'étude
- 8669-001
- AP23573-02-101
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .