Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma
8 de março de 2019 atualizado por: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas
The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma.
A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
The effectiveness of treatments for recurrent sarcomas is quite limited.
One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.
Tipo de estudo
Intervencional
Inscrição (Real)
24
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Maryland
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Baltimore, Maryland, Estados Unidos, 21231
- Johns Hopkins University
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
1 ano e mais velhos (Filho, Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Histologically confirmed sarcoma that is recurrent or refractory to conventional treatment
- Measurable disease by RECIST criteria
- ECOG (Eastern Cooperative Oncology Group) performance status < 2 (or Lansky/Karnofsky > 60% for children)
- Life expectancy greater than 3 months
- Adequate organ function
- absolute neutrophil count at least 1,500
- platelets at least 100,000
- bilirubin less than 1.5 x upper limit of normal
- AST (aspartate aminotransferase) and ALT(alanine aminotransferase) less than 2.5 x upper limit of normal
- creatinine less than 1.5 x upper limit of normal OR creatinine clearance at least 60 ml/min/1.73 m2
- fasting serum cholesterol less than 350
- fasting serum triglycerides less than 400
- PT (prothrombin) or INR (international normalized ratio) less than 1.3 x upper limit of normal
- normal urinalysis
- Ability to understand and sign the informed consent document
Exclusion Criteria:
- Prior chemotherapy or radiotherapy within 3 weeks of entering the study (6 weeks for nitrosoureas or mitomycin C)
- Prior treatment with a tyrosine kinase inhibitor within 10 days of entering the study
- History of pulmonary hypertension or pneumonitis
- Patients may not be receiving other investigational agents
- Prior therapy with rapamycin, rapamycin analogues, or tacrolimus
- Uncontrolled brain metastases
- History of grade 3 or 4 hypersensitivity to macrolide antibiotics
- Concurrent treatment with immunosuppressive agents other than a stable (for more than 2 weeks) dose of corticosteroids
- Uncontrolled intercurrent illness
- Pregnancy or breast feeding
- HIV-positive patients on combination antiretroviral therapy
- Grade 3 or 4 proteinuria
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: temsirolimus plus liposomal doxorubicin
Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.
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Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days.
Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified.
The MTD dose was the standard dose of temsirolimus used for the remainder of the study.
Dose modifications were based on protocol parameters for toxicities.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Part 1: Incidence of Dose Limiting Toxicities
Prazo: End of second 28-day cycle
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Dose limiting toxicities in each dose cohort.
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End of second 28-day cycle
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Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Prazo: up to 5 years
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Number of days from day 1 of treatment until date of death from any cause.
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up to 5 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Prazo: up to 3 years
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Interval from Date of start of treatment to date of disease progression or death from any cause.
Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions.
Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.
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up to 3 years
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Objective Response Rate
Prazo: up to 5 years
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Number of participants who completed at least 2 treatment cycles with evidence of response.
Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
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up to 5 years
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Maximum Observed Plasma Concentration (Cmax)
Prazo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Area Under the Curve (AUC)
Prazo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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AUC was calculated using a single compartment model.
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Drug Clearance
Prazo: Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.
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Prior to the initial dose on day 1, then 2, 6, and 24 hours post dose; prior to first dose of Cycle 2, then at 1, 2, 6, 24, 96, and 120 hours post dose in patients treated at the recommended phase 2 dose, Dose Level 4.
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Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Prazo: up to 3 years
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Interval from start of treatment to disease progression or death from any cause.
Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions.
Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression
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up to 3 years
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Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2
Prazo: up to 5 years
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up to 5 years
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Time to Response
Prazo: up to 5 years
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Number of days after 2 cycles of treatment, until maximal response is observed.
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up to 5 years
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Duration of Response
Prazo: up to 5 years
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Number of days until documentation of disease progression or date of death from other cause
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up to 5 years
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Clinical Benefit Rate
Prazo: up to 5 years
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Number of days from documented improvement to disease progression.
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up to 5 years
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Colaboradores
Investigadores
- Investigador principal: David M Loeb, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- Thornton KA, Chen AR, Trucco MM, Shah P, Wilky BA, Gul N, Carrera-Haro MA, Ferreira MF, Shafique U, Powell JD, Meyer CF, Loeb DM. A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma. Int J Cancer. 2013 Aug 15;133(4):997-1005. doi: 10.1002/ijc.28083. Epub 2013 Mar 4.
- Trucco MM, Meyer CF, Thornton KA, Shah P, Chen AR, Wilky BA, Carrera-Haro MA, Boyer LC, Ferreira MF, Shafique U, Powell JD, Loeb DM. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018 Nov 5;8:21. doi: 10.1186/s13569-018-0107-9. eCollection 2018.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de setembro de 2009
Conclusão Primária (Real)
1 de setembro de 2012
Conclusão do estudo (Real)
1 de setembro de 2012
Datas de inscrição no estudo
Enviado pela primeira vez
28 de julho de 2009
Enviado pela primeira vez que atendeu aos critérios de CQ
29 de julho de 2009
Primeira postagem (Estimativa)
30 de julho de 2009
Atualizações de registro de estudo
Última Atualização Postada (Real)
11 de março de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
8 de março de 2019
Última verificação
1 de março de 2019
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias de Tecidos Conjuntivos e Moles
- Neoplasias por Tipo Histológico
- Neoplasias
- Sarcoma
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Inibidores da Topoisomerase II
- Inibidores da Topoisomerase
- Agentes antibacterianos
- Antibióticos, Antineoplásicos
- Antifúngicos
- Doxorrubicina
- Doxorrubicina lipossomal
- Sirolimo
Outros números de identificação do estudo
- J0963
- NA_00028490 (Outro identificador: JHMI-IRB)
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