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Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma : Protocol of a prospective multicenter phase 2 trial.
Römer, Tristan; Vokuhl, Christian; Staatz, Gundula; Mottaghy, Felix M; Christiansen, Hans; Eble, Michael J; Timmermann, Beate; Klussmann, Jens Peter; Elbracht, Miriam; Calaminus, Gabriele; Zimmermann, Martin; Brümmendorf, Tim H; Feuchtinger, Tobias; Kerp, Helena; Kontny, Udo.
Affiliation
  • Römer T; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany.
  • Vokuhl C; Section of Pediatric Pathology, Department of Pathology, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), University Hospital Bonn, Bonn, Germany.
  • Staatz G; Section of Pediatric Radiology, University Medical Center Mainz, Mainz, Germany.
  • Mottaghy FM; Department of Nuclear Medicine, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany.
  • Christiansen H; Department of Radiotherapy and Radiation Oncology, Hannover Medical School, Hannover, Germany.
  • Eble MJ; Department of Radiation Oncology, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany.
  • Timmermann B; Department of Particle Therapy, West German Proton Therapy Centre Essen (WPE), West German Cancer Centre (WTZ), University Hospital Essen, Essen, Germany.
  • Klussmann JP; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), ENT Clinic of the University Hospital of Cologne, Cologne, Germany.
  • Elbracht M; Institute for Human Genetics and Genomic Medicine, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany.
  • Calaminus G; Division of Pediatric Hematology and Oncology, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), University Hospital Bonn, Bonn, Germany.
  • Zimmermann M; Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Brümmendorf TH; Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany.
  • Feuchtinger T; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Kerp H; Pediatric Research Network gGmbH, University of Duisburg-Essen, Essen, Germany.
  • Kontny U; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), RWTH Aachen University, Aachen, Germany. ukontny@ukaachen.de.
HNO ; 72(6): 423-439, 2024 Jun.
Article in En | MEDLINE | ID: mdl-38214716
ABSTRACT

BACKGROUND:

Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon­ß, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients.

METHODS:

This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression.

DISCUSSION:

As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. TRIAL REGISTRATION EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antineoplastic Combined Chemotherapy Protocols / Nasopharyngeal Neoplasms / Induction Chemotherapy / Nasopharyngeal Carcinoma / Nivolumab Type of study: Clinical_trials / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: HNO Year: 2024 Document type: Article Affiliation country: Alemania Country of publication: Alemania

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antineoplastic Combined Chemotherapy Protocols / Nasopharyngeal Neoplasms / Induction Chemotherapy / Nasopharyngeal Carcinoma / Nivolumab Type of study: Clinical_trials / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Language: En Journal: HNO Year: 2024 Document type: Article Affiliation country: Alemania Country of publication: Alemania