Using Nivolumab with chemotherapy for nasopharyngeal carcinoma in children and adults

Nivolumab in Combination With Cisplatin and 5-Fluorouracil as Induction Therapy in Children and Adults With EBV-positive Nasopharyngeal Carcinoma

This study tests if adding the drug Nivolumab to regular chemotherapy can help children and adults with nasopharyngeal carcinoma respond better to treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 57 (estimated)
• Ages: 3 Years and up
• Sex: All
• Sponsor: German Society for Pediatric Oncology and Hematology GPOH gGmbH (other)
• Drugs / interventions: chemotherapy, prednisone, Nivolumab
• Locations: 31 sites (Aachen and 30 other locations)
• Trial ID: NCT06019130 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of adding the immune checkpoint inhibitor Nivolumab to standard induction chemotherapy in patients with nasopharyngeal carcinoma. Participants will be screened for eligibility and, if qualified, will receive Nivolumab alongside chemotherapy regimens tailored to their age and disease stage. The primary goal is to increase the rate of complete responses as measured by MRI and PET scans after three cycles of treatment. Patients with metastatic disease will continue to receive Nivolumab during subsequent radiochemotherapy.

Who should consider this trial

Good fit: Ideal candidates include children and young adults aged 3 to 25 with newly diagnosed nasopharyngeal carcinoma, as well as adults over 25 with stage III or IV disease.

Not a fit: Patients with stage I nasopharyngeal carcinoma or recurrent disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with nasopharyngeal carcinoma by enhancing response rates to chemotherapy.

How similar studies have performed: Other studies have shown promise with immunotherapy approaches in similar cancers, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II in patients \> 25 years of age
2. Recurrent nasopharyngeal carcinoma
3. Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
4. Prior chemotherapy and/or radiotherapy
5. Other active malignancy
6. 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.
7. The subject received an investigational drug within 30 days prior to inclusion into this study
8. Subjects who are enrolled in another clinical trial
9. Subjects with prior organ allograft or allogenic bone marrow transplantation
10. 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.
11. 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.
12. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14. Inadequate hematologic, renal or hepatic function defined by any of the following screening laboratory values:

    1. WBC \< 2 000/µl
    2. Neutrophils \< 1 500/µl
    3. Platelets \< 100 x 10e3/µL
    4. Hemoglobin \< 9.0 g/dL
    5. Creatinine \>1.5 x ULN or creatinine clearance \< 50 mL/min (using the Cockcroft Gault formula or Schwartz formula in patients \< 18 years)
    6. AST/ALT \> 3 x ULN (\> 5 x ULN if liver metastases)
    7. Total Bilirubin \> 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level ≥ 3.0 x ULN)
15. Hearing loss \> 20 dB loss at 3 kHz due to an inner ear disorder and not caused by tumour burden
16. History of allergy or hypersensitivity to platinum-containing compounds or other study drug components
17. 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).
18. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug.
19. Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lansky score ≥ 60 (age \< 16).
20. 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.
21. 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.
22. 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. (Please refer to section 4.4)
23. Lactating females
24. Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
25. The subject is unwilling or unable to follow the procedures outlined in the protocol
26. The subject is mentally or legally incapacitated.

Where this trial is running

Aachen and 30 other locations

• Uniklinik RWTH Aachen, Department of Internal Medicine — Aachen, Germany (RECRUITING)
• Uniklinik RWTH Aachen, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation — Aachen, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin — Berlin, Germany (ACTIVE_NOT_RECRUITING)
• Evangelisches Klinikum Bethel, Children's Hospital — Bielefeld, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatric Hematology and Oncology, University Hospital — Bonn, Germany (NOT_YET_RECRUITING)
• Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne — Cologne, Germany (RECRUITING)
• Children's Hospital, Carl-Thiem Klinikum Cottbus — Cottbus, Germany (RECRUITING)
• Clinic for Children and Adolescent Medicine, Klinikum Dortmund — Dortmund, Germany (ACTIVE_NOT_RECRUITING)
• Department of Internal Medicine, Klinikum Dortmund — Dortmund, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatrics, University Hospital, Technische Universität Dresden — Dresden, Germany (ACTIVE_NOT_RECRUITING)
• Department fo Radiotherapy, University Hospital — Erlangen, Germany (RECRUITING)
• Department of Pediatrics, University Hospital Erlangen — Erlangen, Germany (ACTIVE_NOT_RECRUITING)
• Department of Medical Oncology, West German Cancer Center, University Hospital Essen — Essen, Germany (NOT_YET_RECRUITING)
• Department of Pediatric Hematology and Oncology, University Hospital Essen — Essen, Germany (NOT_YET_RECRUITING)
• Department of Pediatrics, University Hospital — Frankfurt, Germany (NOT_YET_RECRUITING)
• Department of Pediatric Hematology/Oncology, University Hospital Freiburg — Freiburg im Breisgau, Germany (NOT_YET_RECRUITING)
• Department of Pediatric Oncology, Justus-Liebig University of Giessen — Giessen, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatric Oncology, University Hospital — Göttingen, Germany (NOT_YET_RECRUITING)
• Department of Pediatric Hematology/Oncology, University Medicine Greifswald — Greifswald, Germany (NOT_YET_RECRUITING)
• Universitätsklinikum Halle, Klinik für Pädiatrie I — Halle, Germany (RECRUITING)
• Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, — Hamburg, Germany (RECRUITING)
• Department of Pediatric Oncology, University Children's Hospital — Hamburg, Germany (RECRUITING)
• Department of Otorhinolaryngology, Jena University Hospital — Jena, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatric Oncology, University Hospital Kiel — Kiel, Germany (RECRUITING)
• Department of Pediatrics, University Hospital Mageburg — Magdeburg, Germany (NOT_YET_RECRUITING)
• Pediatric Hematology/Oncology, University Medicine Mainz — Mainz, Germany (ACTIVE_NOT_RECRUITING)
• Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, — Mannheim, Germany (RECRUITING)
• Department of Pediatric Hematology and Oncology, University Children's Hospital — Münster, Germany (ACTIVE_NOT_RECRUITING)
• Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital — Regensburg, Germany (NOT_YET_RECRUITING)
• Universitätsklinikum Tübingen, Klinik für Pädiatrie I — Tübingen, Germany (RECRUITING)
• Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, University of Würzburg — Würzburg, Germany (ACTIVE_NOT_RECRUITING)

Study contacts

• Principal investigator: Udo Kontny, MD — Uniklinik RWTH Aachen
• Study coordinator: Helena Kerp, PhD

Conditions: Nasopharyngeal Carcinoma, Nasopharyngeal Cancer, Nasopharyngeal Neoplasms, Nasopharynx Cancer, Immunotherapy, Nivolumab, Children, Adults