Nivolumab in combination with cisplatin and 5-fluorouracil as induction therapy in children and adults with EBV-positive nasopharyngeal carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GPOH gGmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Dec 2025 → ongoing

Decision date (initial)

2022-08-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

German Cancer Aid

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

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 3

1. To investigate the safety of Nivolumab in combination with standard induction chemotherapy in children and adults with nasopharyngeal carcinoma
2. 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
3. Event-free and overall survival of patients

Conditions and MedDRA coding

EBV-positive nasopharyngeal carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed new diagnosis of nasopharyngeal carcinoma according to the current WHO classification in children and adolescents aged between 3 and 17 years
2. Alternatively to (1): histologically confirmed new diagnosis of EBV-positive nasopharyngeal carcinoma, WHO stage II or III, in subjects ≥ 18 years
3. Stage II or higher in patients ≤ 25 years of age, stage III and IV in patients > 25 years of age (AJCC, 8th edition)
4. Measurable disease by MRI per RECIST 1.1 criteria
5. Written informed consent by legal guardians (if patient not ≥ 18 years) and patient prior to study participation
6. Sufficient tumor tissue to be sent for central review, including PD-L1 staining, either as 2 full blocks or a minimum of 25 slides, obtained from core biopsy, punch biopsy, excisional biopsy or surgical specimen

Exclusion criteria 26

1. Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II in patients > 25 years of age
2. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
3. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
4. Inadequate hematologic, renal or hepatic function
5. Hearing loss > 20 dB loss at 3 kHz
6. History of allergy or hypersensitivity to platinum-containing compounds or other study drug components
7. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening)
8. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug
9. Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lansky score ≥ 60 (age < 16)
10. 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
11. 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
12. Recurrent nasopharyngeal carcinoma
13. Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol
14. Lactating females
15. The subject is unwilling or unable to follow the procedures outlined in the protocol
16. The subject is mentally or legally incapacitated
17. Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
18. Prior chemotherapy and/or radiotherapy
19. Other active malignancy
20. 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
21. The subject received an investigational drug within 30 days prior to inclusion into this study
22. Subjects with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol
23. 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
24. Subjects who are enrolled in another clinical trial
25. Subjects with prior organ allograft or allogenic bone marrow transplantation
26. 24. Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete remission rate (CRR): defined as the proportion of subjects achieving a complete response on MRI and PET/CT after induction chemotherapy with 5-fluorouracil and cisplatin in combination with Nivolumab according to RECIST 1.1 criteria

Secondary endpoints 4

1. Event-free survival (EFS)
2. Overall survival (OS)
3. Safety and tolerability: adverse events (AEs), serious adverse events (SAEs)
4. Efficacy based on PD-L1 expression in tumor tissue

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GPOH gGmbH

Sponsor organisation

GPOH gGmbH

Address

Holsterhauser Platz 2, Holsterhausen Holsterhausen

City

Essen

Postcode

45147

Country

Germany

Scientific contact point

Organisation

Gpoh Gemeinnützige GmbH

Contact name

Prof. Dr. med. Udo Kontny

Public contact point

Organisation

Gpoh Gemeinnützige GmbH

Contact name

Prof. Dr. Dr. Birgit Burkhardt

Third parties 2

Locations

1 EU/EEA country · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications