- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico 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
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
|
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Experimental: 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.
Outros nomes:
|
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Experimental: 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.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
|
Maximum Tolerated Dose (MTD)
Prazo: Cycle 1 (within the first 4 weeks)
|
Cycle 1 (within the first 4 weeks)
|
|
Number of Participants Reporting Adverse Events (AE)
Prazo: 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
Prazo: Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
Best Overall Tumor Response
Prazo: 8 weeks
|
8 weeks
|
|
Maximum Concentration (Cmax) of Ridaforolimus
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças cardiovasculares
- Doenças Vasculares
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Doenças Hematológicas
- Distúrbios hemorrágicos
- Distúrbios hemostáticos
- Paraproteinemias
- Distúrbios das Proteínas Sanguíneas
- Neoplasias de Células Plasmáticas
- Mieloma múltiplo
- Efeitos Fisiológicos das Drogas
- Agentes Anti-Infecciosos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Agentes antibacterianos
- Antibióticos, Antineoplásicos
- Antifúngicos
- Sirolimo
Outros números de identificação do estudo
- 8669-001
- AP23573-02-101
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