- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01975519
A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma
The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated.
The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35243
- University of Alabama at Birmingham
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California
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Santa Monica, California, Estados Unidos, 90403
- Sarcoma Oncology Center
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Mayo Clinic Jacksonville
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic Rochester
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New York
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Buffalo, New York, Estados Unidos, 92122
- Roswell Park Cancer Institute
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New York, New York, Estados Unidos, 10029
- Mount Sinai School of Medicine-Tisch Cancer Institute
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke University
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Texas
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Dallas, Texas, Estados Unidos, 75230
- Mary Crowley Cancer Research Center
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Utah
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Salt Lake City, Utah, Estados Unidos, 84112
- University of Utah
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Histologically confirmed unresectable soft tissue sarcoma that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1b only)
- Histologically confirmed metastatic soft tissue sarcoma that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
- Histologically confirmed locally advanced (e.g. unresectable) or metastatic angiosarcoma that has progressed following treatment with prior systemic therapy. Progression must be documented on or following the most recent systemic therapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity (Phase 2 angiosarcoma cohorts only)
- Measurable disease by RECIST
- Age of 12 years or older (patient must weigh ≥ 40 kg)
- ECOG performance status ≤ 1
- Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia or neuropathy)
- Adequate organ function.
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Available archival tumor specimen of the soft tissue sarcoma that meets inclusion criterion #1, #2 or #3
Exclusion Criteria:
- Prior treatment with TRC105
- Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
- Current treatment on another therapeutic clinical trial
- Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment.
- No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months.
- Patients who have received wide field radiotherapy ≤ 28 days or limited field radiation for palliation < 14 days prior to cycle 1 day 1 or those patients who have not recovered adequately from side effects of such therapy
- Uncontrolled chronic hypertension
- Significant ascites or pericardial or pleural effusion
- History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
- Active bleeding or pathologic condition that carries a high risk of bleeding. Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
- Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
- Known active viral or nonviral hepatitis or cirrhosis
- History of hemorrhage or hemoptysis within 3 months of starting study treatment
- History of peptic ulcer within the past 3 months of treatment
- History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Receipt of a strong CYP3A4 inducer within 12 days prior to cycle 1 day 1 or a strong CYP3A4 inhibitor within 7 days prior to cycle 1 day 1.
- Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.
Plano de estudo
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: TRC105 and Pazopanib
Weekly TRC105 in combination with standard dose pazopanib or every two week administration during cycle 1, and starting on cycle 2 day 1 and beyond, TRC105 may be administered every two weeks.
This is also in combination with standard dose pazopanib.
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Weekly TRC105 in combination with standard dose Pazopanib.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Number of Participants With Dose Limiting Toxicity (DLT)
Prazo: 56 days
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For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0).
DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, febrile neutropenia (grade 4 neutropenia with fever > 38.5 ºC both sustained over a 24 hour period), neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, grade > 4 thrombocytopenia or grade ≥ 3 thrombocytopenia and grade ≥ 3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: nausea, vomiting, or diarrhea for <48 hours, asymptomatic electrolyte abnormalities that are corrected to grade 1 or better in < 72 hours, or headache lasting less than 48 hours.
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56 days
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Progression Free Survival of Patients With Advanced Soft Tissue Sarcoma (Phase 1 and 2)
Prazo: from screening to either disease progression or death
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Number of patients with progression free survival, as defined as time from screening to either first disease progression or death from any cause per RECIST version 1.1
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from screening to either disease progression or death
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Objective Response Rate in a Cohort of Patients With Angiosarcoma
Prazo: 1.5 years
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The best response according to RECIST 1.1 for each patient in the phase 2 angiosarcoma cohort with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type
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1.5 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Trough Concentrations of TRC105 (Phase 2)
Prazo: 4, 6, 8, and 10 weeks
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Trough serum TRC105 concentrations will be measured using validated ELISA methods.
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4, 6, 8, and 10 weeks
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Number of Patients With and Without Development of Immunogenicity Antibodies (Phase 1 and 2)
Prazo: 32 months
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Anti-product antibody concentrations will be measured using validated ELISA methods.
Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.
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32 months
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Number of Patients With and Without Expression of Endoglin on Sarcoma Tissue (Phase 1 and 2)
Prazo: 12 months
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Expression will be determined by immunohistochemistry for each patient who received at least one dose of TRC105
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12 months
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Objective Response Rate in Patients With Advanced Soft Tissue Sarcoma by RECIST 1.1
Prazo: 12 months
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The best response (CR, PR, SD or PD according to RECIST 1.1) for each patient (phase 1 and phase 2) with measurable disease who received at least one dose of TRC105 study drug
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12 months
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Progression Free Survival in a Cohort of Patients With Angiosarcoma (Phase 2)
Prazo: 26 months
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Time from screening to either first disease progression or death from any cause per RECIST version 1.1
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26 months
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
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 (Real)
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
Outros números de identificação do estudo
- 105SAR101
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
Ensaios clínicos em TRC105 and Pazopanib
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Centre Leon BerardGlaxoSmithKlineConcluídoCarcinoma de TireóideFrança
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National Cancer Institute (NCI)ConcluídoCarcinoma Urotelial | Neoplasias ureterais | Câncer de Ureter | Câncer do Ureter | Neoplasia UreteralEstados Unidos
-
Tracon Pharmaceuticals Inc.ConcluídoCarcinoma de Trompas de Falópio | Carcinoma Peritoneal Primário | Câncer de ovário recorrenteEstados Unidos
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National Cancer Institute (NCI)ConcluídoCâncer de próstata | Câncer de Próstata Metastático Resistente à CastraçãoEstados Unidos
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University Hospitals Cleveland Medical CenterDesconhecidoAsma | Rinite alérgica | Conjuntivite alérgicaEstados Unidos
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National Cancer Institute (NCI)ConcluídoCarcinoma Hepatocelular | Carcinoma hepatocelular | Câncer HepatocelularEstados Unidos
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Tracon Pharmaceuticals Inc.RescindidoCarcinoma de Células RenaisEstados Unidos, Hungria, Tcheca, Reino Unido
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University of Alabama at BirminghamTracon Pharmaceuticals Inc.ConcluídoCâncer de pulmãoEstados Unidos
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John SappNova Scotia Health Authority; Rochester Institute of TechnologyRecrutamentoInfarto do miocárdio | Taquicardia ventricularCanadá
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Tracon Pharmaceuticals Inc.ConcluídoAngiossarcoma AvançadoEstados Unidos, França, Itália, Áustria, Alemanha, Polônia, Espanha, Reino Unido