- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00544817
Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme
The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).
In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.
Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.
After completion of combined modality therapy, patients will have 4 weeks without any therapy.
Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Florida
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Fort Myers, Florida, Estados Unidos, 33901
- Florida Cancer Specialists
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Georgia
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Gainesville, Georgia, Estados Unidos, 30501
- Northeast Georgia Medical Center
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Maryland
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Bethesda, Maryland, Estados Unidos, 20817
- Center for Cancer and Blood Disorders
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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- Grand Rapids Clinical Oncology Program
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68114
- Methodist Cancer Center
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45242
- Oncology Hematology Care
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South Carolina
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Spartanburg, South Carolina, Estados Unidos, 29303
- Spartanburg Regional Medical Center
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Tennessee Oncology
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Texas
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San Antonio, Texas, Estados Unidos, 78258
- South Texas Oncology and Hematology
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Virginia
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Richmond, Virginia, Estados Unidos, 23235
- Virginia Cancer Institute
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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 intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
- ECOG performance status 0 or 1 (See Appendix C)
- Age ≥ 18 years
- Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥ 100,000/μL.
Adequate liver function
- Total bilirubin ≤ 1.5 x ULN
- ALT and AST ≤ 2.5 x ULN
- Serum creatinine < 1.5 x ULN
- Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women must agree to not breast feed while receiving study treatment.
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment. Women should use adequate birth control for at least 3 months after the last administration of sorafenib.
- INR < 1.5 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Patients must have the ability to understand and the willingness to sign written informed consent. A signed informed consent must be obtained prior to any study-specific procedures.
Exclusion Criteria:
- Patients must have the ability to swallow whole pills.
- Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D); unstable angina or new onset angina within the last 3 months; myocardial infarction within the last 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
- Active clinically serious infection > grade 2
- Thrombotic or embolic events including cerebral vascular accident or TIAs within the past 6 months
- Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of sorafenib
- Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of sorafenib
- Serious non-healing wound, ulcer, or bone fracture
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy, or significant traumatic injury within 4 weeks of beginning treatment with sorafenib
- Use of St. John's Wort or rifampicin
- Known or suspected allergy to sorafenib or temozolomide
- Any malabsorption problem
- Other active malignancies, or treatment for invasive cancer within the last 2 years
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: Combination Therapy
In the combined modality portion of the study, patients were administered: Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily Patients took a four week break before beginning follow-up systemic therapy: Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months |
2 Gy/fraction, single daily fractions M-F, to 60 Gy total
In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles
Outros nomes:
In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Progression-free Survival
Prazo: 18 months
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Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
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18 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Overall Survival
Prazo: 18 months
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Defined as Day 1 of protocol treatment to date of death from any cause.
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18 months
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Objective Response
Prazo: every 8 weeks until disease progression, estimated 18 months
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The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria. The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD). Criteria: CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved. PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved. SD: does not qualify for complete response, partial response or progression. Clinically stable. PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration. |
every 8 weeks until disease progression, estimated 18 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Cadeira de estudo: John D. Hainsworth, M.D., SCRI Development Innovations, LLC
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
- Neoplasias por Tipo Histológico
- Neoplasias
- Neoplasias Glandulares e Epiteliais
- Astrocitoma
- Glioma
- Neoplasias Neuroepiteliais
- Tumores Neuroectodérmicos
- Neoplasias, Células Germinativas e Embrionárias
- Neoplasias, Tecido Nervoso
- Glioblastoma
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Agentes Antineoplásicos Alquilantes
- Agentes Alquilantes
- Inibidores de proteína quinase
- Temozolomida
- Sorafenibe
Outros números de identificação do estudo
- SCRI CNS 09
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 .
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