Author:  Juia Dobke, Last modification: 2023/03/01

Nivolumab-NPC Nivolumab in combination with cisplatin and 5-flurouracil as induction therapy in children and adults with EBV-positive nasopharyngeal carcinoma
Disease EBV-positive nasopharyngeal carcinoma
Type Multicentre, prospective, single-arm, phase II trial
Problem / Objectives

Primary objective

To increase the percentage of NPC patients with complete response (CR) on magnetic resonance imaging (MRI) and PET-CT after induction chemotherapy, thereby allowing to reduce the dosage of radiotherapy from 59.4 Gy to 54 Gy in in children, adolescents and young adults ≤ 25 years with locoregional disease

Secondary objectives

  • To investigate the safety of Nivolumab in combination with standard induction chemotherapy consisting of cisplatin and 5-fluorouracil in children and adults with nasopharyngeal carcinoma
  • To investigate the safety of Nivolumab in combination with radiochemotherapy in children and adults with nasopharyngeal carcinoma not responding to induction therapy or with metastases
Therapy / Study arms

All patients until 25 years will receive Nivolumab (4,5 mg/kg BW) every 3 weeks added to standard induction chemotherapy (3 blocks of cisplatin/5-fluorouracil). In patients not responding to induction chemotherapy or patients with initial metastatic desease, the application of Nivolumab will be extended to the period of radiochemotherapy.
Patients until 25 years with CR after inductiontherapy will receive radiotherapy with a dose of 54 Gy, all other patients until 25 years of age will receive radiotherapy with a dose of 59,4 Gy.
Following the radiochemotherapy all patients until 25 years of age will receive Interferon-beta for 26 weeks.

Inclusion Criteria
  • Histologically confirmed new diagnosis of nasopharyngeal carcinoma in patients from 3 to 17 years of age or histologically confirmed new diagnosis of EBV-positive nasopharyngeal carcinoma, WHO stage II or III, in subjects of 18 years of age or older
  • Stage II or higher in patients ≤ 25 years of age, stage III and IV in patients > 25 years of age (AJCC, 8th edition)
  • Measurable disease by MRI per RECIST 1.1 criteria
  • Written informed consent by legal guardians (if patient not ≥ 18 years) and patient prior to study participation
Exclusion Criteria
  • Newly diagnosed nasopharyngeal carcinoma, Stage I, recurrent nasopharyngeal carcinoma, nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
  • Prior chemotherapy and/or radiotherapy
  • Other active malignancy
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • The subject received an investigational drug within 30 days prior to inclusion into this study
  • Subjects with an active, known or suspected autoimmune disease.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before start of therapy. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Inadequate hematologic, renal or hepatic function
  • Hearing loss > 20dB loss at 3kHz
  • History of allergy or hypersensitivity to platinum-containing compounds or other study drug components
  • The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
  • The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study
  • Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing. Participants of childbearing age should use adequate contraception as defined in the study protocol.
  • Lactating females
  • The subject is unwilling or unable to follow the procedures outlined in the protocol
  • The subject is mentally or legally incapacitated.
Recruitment 57
Status Duration: 36 month after inclusion of the first patient, Start january 2023
EudraCT 2021-006477-32
Entry Study Register
Principal Investigator Prof. Dr. med. U. Kontny

Principal Investigator

Prof. Dr. Udo Kontny Klinik für Kinder- und Jugendmedizin Universitätsklinikum Aachen Sektion Pädiatrische Onkologie und Stammzelltransplantation Pauwelsstraße 30 52074 Aachen Telefon +49 (241) 80 88892/89902 Fax +49 (241) 80 82481

Participants Participants: 35 German study sites
Sponsoring Deutsche Krebshilfe, Sponsor: Sponsor: GPOH gGmbH, Bristol-Myers Squibb will provide Nivolumab for free