Traiter le cancer de la vessie envahissant les muscles avec une méthode non chirurgicale consistant en une thérapie anti-PD-1 et une chimioradiothérapie (BCIRT-01)
Un essai clinique de phase II à un seul bras pour traiter le cancer de la vessie envahissant les muscles avec une chimiothérapie d'induction plus une thérapie anti-PD-1 suivie d'une radiothérapie plus une thérapie anti-PD-1 simultanée
The goal of this Phase 2 trial is to evaluate a non-surgical bladder-preserving treatment mode which consists of neoadjuvant chemotherapy plus anti-programmed cell death protein 1 (anti-PD-1) therapy followed by radiotherapy plus concurrent anti-PD-1 therapy. The main questions it aims to answer are: (i) whether the anti-PD-1 antibody, toripalimab, is effective in treating muscle-invasive bladder cancer (MIBC), when combined with chemoradiation; (ii) whether toripalimab is safe in combination with chemoradiation. Participants will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy plus 2 cycles of concurrent toripalimab.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Bladder cancer is the second most common malignancies over the world. At initial diagnosis, the cases with muscle-invasive bladder cancer (MIBC) accounts nearly 20% of all bladder cancer patients. And 40% of non-muscle-invasive bladder cancer could develop to MIBC. Currently, radical cystectomy (RC) is the golden standard to manage MIBC. Yet, it brings severe surgical injuries and post-surgical complications which impair life quality of the patients. Recently, bladder-preserving treatment based gradually becomes the second choice for MIBC. It consists of maximal transurethral resection of bladder tumor (TURBT) and chemoradiation. A series of clinical trials and meta-analyses supported that the bladder-preserving treatment has a similar therapeutic effect compared with RC. But it is noteworthy that this treatment mode does not really avoid surgery. TURBT could also cause complications, such as haemorrhage, infection, perforation, and even tumor dissemination. Moreover, the incidence of serious toxicities brought by concurrent chemoradiation is as high as 36%. In actual clinical work, it is hard for more than half patients to complete chemoradiation of standard intensity. Additionally, many patients are unsuitable for bladder preservation, including those with T stage > T2, diameter > 5 cm, hydronephrosis and positive lymph nodes. Hence, it calls for improvement of current bladder preservation mode, to make more MIBC patients receive radical treatment which brings better therapeutic experience and life quality.
Many lab studies indicated that formation and progression of bladder cancer is a process of mutation accumulation. It provides biological fundamentals for immune checkpoint inhibitors, such as anti-programmed cell death protein 1 (anti-PD-1) antibodies. Based on available clinical studies, anti-PD-1 antibodies exhibits ideal therapeutic effects in bladder cancer of different stages and has an incidence of toxicities as low as 13%. Its toxicities mainly include arthralgia and hyponatremia, which are well tolerated. Currently, there are more than 10 clinical trials trying anti-PD-1 antibodies for bladder preservation. However, the treatment modes in most of them still contain TURBT. This phase 2 trial intended to evaluate the therapeutic and adverse effects of a non-surgical bladder-preserving treatment mode consisting of anti-PD-1 antibodies and chemoradiation, in a small patient cohort with MIBC. The results might provide an effective, non-invasive and low-toxic choice which improves patient experience and realizes bladder preservation.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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Guangdong
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Guangzhou, Guangdong, Chine, 510060
- Cancer Center, Sun Yat-sen University
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Pathologically diagnosed bladder malignant tumor via biopsy
- Urothelial carcinoma as the primary histological component
- Pretreatment clinical TNM stage as T2-4aN0-2M0 (UICC TNM staging classification, version 8)
- Age between 18 and 75 years old
- Karnofsky performance score ≥ 70
- Creatinine clearance rate ≥ 30 ml/min
Exclusion Criteria:
- Simultaneous tumors of the urethra or upper urinary tract
- Existence of small cell cancer component
- Uncontrolled tuberculosis, viral hepatitis or AIDS
- Autoimmune or mental diseases
- Severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for chemotherapy, radiotherapy or immune checkpoint inhibiting therapy
- Prior history of other malignancies within 5 years, except cured cervical carcinoma in situ and skin basal cell carcinoma
- Prior history of pelvic radiotherapy or chemotherapy
- Poor adherence to regular follow-up (cystoscopy, CT, MRI, etc.)
- Pregnant or lactating women
- Treatment with glucocorticoid or immunosuppressive drugs within 1 month
- Other situations for which the investigators consider a patient inappropriate to participate
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Toripalimab plus chemoradiation
This study has only single arm in which the patients will receive neoadjuvant chemotherapy plus anti-PD-1 therapy (toripalimab), followed by radiotherapy plus concurrent anti-PD-1 therapy |
The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Toripalimab: 240 mg on Day 1, every 3 weeks, totally 3 and 2 cycles in the neoadjuvant and concurrent phases, respectively.
Autres noms:
The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Gemcitabine: 1 g/m2 on Days 1 and 8, repeated every 3 weeks, totally 3 cycles. The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Cisplatin: Used when creatinine clearance rate ≥ 40 ml/min, 37.5 mg/m2 on Days 1 and 2, repeated every 3 weeks, totally 3 cycles. The patients in this arm will receive 3 cycles of induction treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Cisplatin: Used when creatinine clearance rate < 40 ml/min, area under curve = 2 on Days 1 and 2, repeated every 3 weeks, totally 3 cycles. The patients in this arm will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy, plus 2 cycles of concurrent toripalimab. Radiotherapy: performed by using the technique of intensity-modulated radiation therapy, with a total dose of 65 and 45 Gy for the gross tumor and lymphatic drainage regions. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Clinical complete response (cCR) rate
Délai: When the eligible patients complete the treatment and followed-up for half a year
|
The percentage of the cases attaining cCR of primary tumor and regional lymph nodes (confirmed by radiologic examinations, such as thoraco-bdominal computed tomography, pelvic magnetic resonance imaging, and multipoint biopsy under cystoscopy) |
When the eligible patients complete the treatment and followed-up for half a year
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Overall survival (OS)
Délai: When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
The percentage of the cases surviving over a given time period |
When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
|
Bladder-intact event-free survival (BI-EFS)
Délai: When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
The percentage of the cases surviving with intact bladder and without muscle-invasive recurrence, regional lymph node recurrence or distant metastasis, over a given time period |
When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
|
Disease-free survival (DFS)
Délai: When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
The percentage of the cases surviving without locoregional recurrence or distant metastasis over a given time period |
When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
|
Local recurrence (LR) rate
Délai: When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
The percentage of the cases with locoregional recurrence over a given time period |
When the eligible patients complete the treatment and followed-up for 1 and 2 years
|
|
Incidence of grade 3/4 (G3/4) toxicities
Délai: Once a week during treatment, and once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
The percentage of the cases with any G3/4 toxicity during and after treatment |
Once a week during treatment, and once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
|
Bladder function
Délai: Once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
The quantitative score of bladder function at a given time point, based on the Quality of Life 30-item Questionnaire, Bladder Module (QLQ-BLM30) from the EORTC |
Once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
|
Objective response rate (ORR)
Délai: A week before radiotherapy, and once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
The percentage of the cases attaining clinical complete or partial response of primary tumor and regional lymph nodes (confirmed by radiography and cystoscopy) |
A week before radiotherapy, and once per 3 months after treatment, until the last follow-up (2 years after treatment)
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Yuanhong Gao, MD, Sun Yat-sen University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies urogénitales
- Tumeurs urogénitales
- Tumeurs par site
- Tumeurs
- Maladies urogénitales masculines
- Maladies urologiques
- Maladies urogénitales féminines
- Maladies urogénitales féminines et complications de la grossesse
- Tumeurs urologiques
- Maladies de la vessie urinaire
- Tumeurs de la vessie urinaire
- Produits chimiques organiques
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Thérapeutique
- Produits chimiques inorganiques
- Composés de chlore
- Composés d'azote
- Complexes de coordination
- Désoxycytidine
- Cytidine
- Nucléosides pyrimidine
- Pyrimidines
- Composés en platine
- Radiothérapie
- Radiothérapie, conforme
- Radiothérapie, assistée par ordinateur
- Gemcitabine
- Carboplatine
- Cisplatine
- toripalimab
- Radiothérapie, intensité modulée
Autres numéros d'identification d'étude
- 2023-FXY-068
Informations sur les médicaments et les dispositifs, documents d'étude
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