Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer
15 de maio de 2018 atualizado por: Radiation Therapy Oncology Group
A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of combination chemotherapy plus radiation therapy with or without surgery is more effective in treating bladder cancer.
PURPOSE: Randomized phase II trial to study the effectiveness of two combination chemotherapy regimens and radiation therapy with or without radical cystectomy in treating patients who have stage II or stage III bladder cancer.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
OBJECTIVES:
- Estimate the safety and tolerability of induction paclitaxel, cisplatin, and radiotherapy or fluorouracil, cisplatin, and radiotherapy followed by consolidation chemoradiotherapy or radical cystectomy and adjuvant gemcitabine, paclitaxel, and cisplatin in patients with operable stage II or III bladder cancer.
- Estimate the efficacy of these regimens, in terms of complete response, in patients who have undergone prior transurethral resection (TUR).
- Estimate the efficacy of these regimens after TUR, in terms of preserving the native tumor-free bladder 5 years after therapy, in these patients.
- Estimate the function of the preserved bladder in patients treated with these regimens after TUR.
- Determine the value of tumor histopathologic, molecular genetic, and DNA content parameters as possible prognostic factors for initial tumor response and recurrence-free survival in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T stage (T2 vs T3/T4 ). Patients are randomized to one of two treatment arms.
Induction therapy (weeks 1-3):
- Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also receive pelvic radiotherapy twice daily on days 1-5, 8-12, and 15-17.
- Arm II: Patients receive fluorouracil IV over 24 hours on days 1-3 and 15-17 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also receive pelvic radiotherapy as in arm I.
Patients in both arms who achieve complete response after induction therapy proceed to consolidation therapy on week 8. Patients with operable pT1 or worse tumor response proceed to radical cystectomy on week 9.
Consolidation therapy (weeks 8 and 9):
- Arm I: Patients receive paclitaxel IV over 1 hour on days 1 and 8 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also receive pelvic radiotherapy twice daily on days 1-5 and 8-10.
- Arm II: Patients receive 5-FU IV over 24 hours on days 1-3 and 8-10 and cisplatin as in arm I. Patients also receive radiotherapy as in arm I.
- Adjuvant chemotherapy (weeks 21-33 or 17-29): Beginning 12 weeks after consolidation therapy or 8 weeks after radical cystectomy, patients receive gemcitabine IV over 30-60 minutes, paclitaxel IV over 1 hour, and cisplatin IV over 1 hour on days 1 and 8. Treatment repeats every 3 weeks for 4 courses.
Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 96 patients (48 per treatment arm) will be accrued for this study within 3 years.
Tipo de estudo
Intervencional
Inscrição (Real)
97
Estágio
- Fase 2
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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Utah
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Salt Lake City, Utah, Estados Unidos, 84103
- LDS Hospital
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Salt Lake City, Utah, Estados Unidos, 84106
- Utah Cancer Specialists at UCS Cancer Center
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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
Não mais velho que 120 anos (Filho, Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
DISEASE CHARACTERISTICS:
Histologically confirmed operable primary muscle invasive bladder cancer
- T2-T4a, NX or N0, M0 (stage II or III)
- Must have an adequate functioning bladder
- Must have undergone a prior transurethral resection of the bladder tumor within the past 8 weeks
- No evidence of tumor-related hydronephrosis
- No evidence of distant metastases or histologically or cytologically confirmed lymph node metastases
Patients with involvement of the prostatic urethra with transitional cell cancer that was visibly completely resected are allowed
- No evidence of stromal invasion of the prostate
PATIENT CHARACTERISTICS:
Age
- Not specified
Performance status
- Zubrod 0-1
Life expectancy
- Not specified
Hematopoietic
- Hemoglobin at least 10 g/dL
- White blood cell (WBC) count at least 4,000/mm^3
- Absolute neutrophil count at least 1,800/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Serum bilirubin no greater than 2.0 mg/dL
Renal
- Serum creatinine no greater than 1.5 mg/dL
- Creatinine clearance at least 60 mL/min NOTE: If the creatinine clearance is greater than 60 mL/min, creatinine of no greater than 1.8 mg/dL is allowed at the discretion of the study chair
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except nonmelanoma skin cancer, stage T1a prostate cancer, or carcinoma in situ of the cervix
- Must be able to tolerate systemic chemotherapy with pelvic radiotherapy and radical cystectomy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior systemic chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior pelvic radiotherapy
Surgery
- See Disease Characteristics
Other
- No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycosides)
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: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Pelvic RT + paclitaxel + cisplatin
Induction: Twice-daily pelvic radiation therapy (RT) with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin.
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Induction: 15 mg/m2 as a 60-minute infusion on days 1, 2, 3, 8, 9, 10, 15, 16, and 17; Consolidation: 15 mg/m2 as a 60-minute infusion on days 1, 2, 8, and 9; Adjuvant: 35 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.
Induction: 50 mg/m2 as a 60-minute infusion on days 1, 8, and 15; Consolidation: 50 mg/m2 as a 60-minute infusion on days 1 and 8; Adjuvant: 50 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.
Induction: External beam irradiation, 1.6 Gy, will be given to the pelvis in the first treatment followed by an interfraction period of at least 4-6 hours.
During the second treatment, 1.5 Gy will be delivered to the whole bladder for the first five sessions (7.5 Gy) then to the tumor plus a margin for eight sessions (12.
Gy).
Consolidation: Consolidation therapy will start 7-14 days following a cystoscopic re-evaluation demonstrating a complete response to the induction therapy.
1.5 Gy (per fraction) will be given to the pelvis in two treatment fractions per day, with an interfraction period of at least 4-6 hours.
Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.
Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.
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Experimental: Pelvic RT + fluorouracil + cisplatin
Induction: Twice-daily pelvic radiation therapy (RT) with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin.
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Induction: 15 mg/m2 as a 60-minute infusion on days 1, 2, 3, 8, 9, 10, 15, 16, and 17; Consolidation: 15 mg/m2 as a 60-minute infusion on days 1, 2, 8, and 9; Adjuvant: 35 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.
Induction: External beam irradiation, 1.6 Gy, will be given to the pelvis in the first treatment followed by an interfraction period of at least 4-6 hours.
During the second treatment, 1.5 Gy will be delivered to the whole bladder for the first five sessions (7.5 Gy) then to the tumor plus a margin for eight sessions (12.
Gy).
Consolidation: Consolidation therapy will start 7-14 days following a cystoscopic re-evaluation demonstrating a complete response to the induction therapy.
1.5 Gy (per fraction) will be given to the pelvis in two treatment fractions per day, with an interfraction period of at least 4-6 hours.
Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.
Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.
Induction: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 15, 16, and 17; Consolidation: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 8, 9, and 10.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Treatment Completion Rate
Prazo: From randomization to 11 weeks
|
Radiation therapy and chemotherapy per protocol or within acceptable variation guidelines based on central review.
The study was designed for a two-sided binomial test with 87% power and a significance level of 0.05 with a null hypothesis of a 70% completion rate against the alternative 90% completion rate.
For each arm, more than 34 out of 43 evaluable patients completing the treatment, would indicate to reject the null hypothesis for a better treatment completion rate.
Fewer than 24 out 43 evaluable patients completing the treatment would indicate to reject the null hypothesis for a worse treatment completion rate.
Otherwise, the conclusion would be that there is not enough evidence to reject the null hypothesis of a 70% completion rate in either direction.
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From randomization to 11 weeks
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Complete Response After Induction
Prazo: From randomization to eight weeks
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Complete response requires the absence of any tumor in the tumor-site biopsy specimen or elsewhere and a bimanual exam that does not indicate the presence of a tumor mass.
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From randomization to eight weeks
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Bladder-intact Survival Rate (5 Years)
Prazo: From the date of randomization to five years.
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Bladder-intact survival was measured from the date of randomization to occurrence of cystectomy or death.
Five-year rates were estimated using the Kaplan-Meier method.
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From the date of randomization to five years.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Cadeira de estudo: Robert Dreicer, MD, FACP, The Cleveland Clinic
- Investigador principal: Anthony L. Zietman, MD, Massachusetts General Hospital
- Cadeira de estudo: Robert Uzzo, MD, Fox Chase Cancer Center
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
- Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. doi: 10.1200/JCO.2014.57.5548. Epub 2014 Nov 3. Erratum In: J Clin Oncol. 2015 Mar 1;33(7):814.
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.
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 (Real)
1 de dezembro de 2002
Conclusão Primária (Real)
1 de outubro de 2010
Conclusão do estudo (Real)
14 de maio de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
6 de março de 2003
Enviado pela primeira vez que atendeu aos critérios de CQ
6 de março de 2003
Primeira postagem (Estimativa)
7 de março de 2003
Atualizações de registro de estudo
Última Atualização Postada (Real)
15 de junho de 2018
Última atualização enviada que atendeu aos critérios de controle de qualidade
15 de maio de 2018
Última verificação
1 de maio de 2018
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias
- Neoplasias Urológicas
- Neoplasias urogenitais
- Neoplasias por local
- Doenças Urológicas
- Doenças da Bexiga Urinária
- Neoplasias da Bexiga Urinária
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Antivirais
- Inibidores Enzimáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Moduladores de Tubulina
- Agentes Antimitóticos
- Moduladores de Mitose
- Agentes Antineoplásicos Fitogênicos
- Gemcitabina
- Paclitaxel
- Cisplatina
- Fluorouracil
Outros números de identificação do estudo
- RTOG 0233
- CDR0000258303
- ECOG-R0233
- NCI-2011-01578 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
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 .