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Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer

15 mai 2018 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

97

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Utah
      • Salt Lake City, Utah, États-Unis, 84103
        • LDS Hospital
      • Salt Lake City, Utah, États-Unis, 84106
        • Utah Cancer Specialists at UCS Cancer Center

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

Pas plus vieux que 120 ans (Enfant, Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: cisplatin
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.
Médicament: paclitaxel
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.
Radiation: radiation therapy
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.
Médicament: Gemcitabine
Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.
Procédure: Radical cystectomy
Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.
Expérimental: 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.
Médicament: cisplatin
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.
Radiation: radiation therapy
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.
Médicament: Gemcitabine
Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.
Procédure: Radical cystectomy
Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.
Médicament: fluorouracil
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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Treatment Completion Rate
Délai: 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.
From randomization to 11 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Complete Response After Induction
Délai: From randomization to eight weeks
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.
From randomization to eight weeks
Bladder-intact Survival Rate (5 Years)
Délai: From the date of randomization to five years.
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.
From the date of randomization to five years.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Radiation Therapy Oncology Group

Collaborateurs

National Cancer Institute (NCI)
NRG Oncology
Eastern Cooperative Oncology Group

Les enquêteurs

  • Chaise d'étude: Robert Dreicer, MD, FACP, The Cleveland Clinic
  • Chercheur principal: Anthony L. Zietman, MD, Massachusetts General Hospital
  • Chaise d'étude: Robert Uzzo, MD, Fox Chase Cancer Center

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 décembre 2002

Achèvement primaire (Réel)

1 octobre 2010

Achèvement de l'étude (Réel)

14 mai 2018

Dates d'inscription aux études

Première soumission

6 mars 2003

Première soumission répondant aux critères de contrôle qualité

6 mars 2003

Première publication (Estimation)

7 mars 2003

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

15 juin 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 mai 2018

Dernière vérification

1 mai 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • RTOG 0233
  • CDR0000258303
  • ECOG-R0233
  • NCI-2011-01578 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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