Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756).

Humans Cisplatin Carboplatin / therapeutic use Gemcitabine Carcinoma, Transitional Cell / pathology Neoadjuvant Therapy / methods Retrospective Studies Urinary Bladder Neoplasms / drug therapy Kidney Neoplasms / pathology Ureteral Neoplasms / drug therapy Antibodies, Monoclonal / therapeutic use Kidney Pelvis / pathology Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Durvalumab Neoadjuvant chemotherapy Neoadjuvant immunotherapy Nephroureterectomy Upper tract urothelial cancer

Journal

World journal of urology
ISSN: 1433-8726
Titre abrégé: World J Urol
Pays: Germany
ID NLM: 8307716

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 27 03 2023
accepted: 23 08 2023
medline: 4 12 2023
pubmed: 12 9 2023
entrez: 12 9 2023
Statut: ppublish

Résumé

Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

Sections du résumé

BACKGROUND BACKGROUND
Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer.
STUDY DESIGN AND ENDPOINTS UNASSIGNED
Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned.
PATIENTS AND INTERVENTIONS METHODS
Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

Identifiants

DOI: 10.1007/s00345-023-04596-5 PMID: 37698632
pubmed: 37698632
doi: 10.1007/s00345-023-04596-5
pii: 10.1007/s00345-023-04596-5
doi:

Substances chimiques

Cisplatin Q20Q21Q62J
Carboplatin BG3F62OND5
Gemcitabine 0
durvalumab 28X28X9OKV
Antibodies, Monoclonal 0

Banques de données

ClinicalTrials.gov
['NCT04617756']

Types de publication

Clinical Trial, Phase III Randomized Controlled Trial Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3413-3420

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

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Auteurs

Giorgio Calleris (G)

GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 75013, Paris, France.
Department of Surgical Sciences, Urology, University of Turin, Turin, Italy.

Morgan Rouprêt (M)

GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 75013, Paris, France. mroupret@gmail.com.

Thomas Seisen (T)

GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 75013, Paris, France.

Lyamin Bendjeddou (L)

Research and Innovation Department, Nimes University Hospital, 30029, Nimes, France.

Thierry Chevallier (T)

Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology (BESPIM), Nimes University Hospital, 30029, Nimes, France.
UMR 1302, Institute Desbrest of Epidemiology and Public Health, INSERM, Univ. Montpellier, Montpellier, France.

Alexandra Masson-Lecomte (A)

Department of Urology, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, 75010, Paris, France.

Constance Thibault (C)

Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hopital Européen Georges Pompidou, Paris, France.

Yann Neuzillet (Y)

Department of Urology, Foch Hospital, Paris Saclay University, Suresnes, France.

François Audenet (F)

Department of Urology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.

Evanguelos Xylinas (E)

Service d'Urologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.

Nadine Houédé (N)

Gard Cancer Institute, Nimes University Hospital, University of Montpellier, 30029, Nimes, France.

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