Nivolumab in Children and Adults With Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

— NPC-Nivo  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06019130
• Other study ID #: EUCT: 2022-500676-59-00
• Status: Recruiting
• Phase: Phase 2
• Start date: January 10, 2023
• Est. completion date: January 9, 2028

Study information

• Verified date: August 2023
• Source: German Society for Pediatric Oncology and Hematology GPOH gGmbH
• Contact: Helena Kerp, PhD
• Phone: +49 201 74 94 96 14
• Email: h.kerp[@]forschung-paediatrie.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess whether the addition of the immune checkpoint inhibitor Nivolumab to induction chemotherapy will increase the percentage of patients with a complete response on MRI and PET after 3 cycles of induction therapy.

Description:

After being informed about the study and potential risks, all patients will undergo a 2-week screening period to determine eligibility for study entry. After informed consent has been obtained, all patients ≤ 25 years and patients > 25 years without metastases will receive Nivolumab (4.5 mg/kg BW (max. 360 mg) q 3 weeks) added to standard induction chemotherapy (3 blocks of cisplatin/5-fluorouracil). In patients not responding to induction chemotherapy, the application of Nivolumab will be extended throughout the period of radiochemotherapy. Patients > 25 years with metastatic disease will receive Nivolumab (4.5 mg/kg BW (max. 360 mg) q 3 weeks) added to induction chemotherapy with 3 blocks of cisplatin/gemcitabine. All patients with metastatic disease will continue to receive Nivolumab during radiochemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 57
• Est. completion date: January 9, 2028
• Est. primary completion date: January 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Cancer
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms
• Nasopharynx Cancer

Intervention

Drug:
• Nivolumab
Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases
• Cisplatin
Cisplatin during induction chemotherapy and during radiochemotherapy in all groups
• 5-Fluorouracil
5-Fluoruracil during induction chemotherapy in all groups except of adults > 25 years with metastatic disease at diagnosis
• Gemcitabine
Gemcitabine during induction chemotherapy in patients > 25 years with metastatic disease at diagnosis

Radiation:
• Radiotherapy
After induction therapy in all patients

Drug:
• Interferon beta-1a
In patients < 26 years after end of radiochemotherapy for 6 months

Procedure:
• MRI
At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy
• PET
At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy, either as PET-CT or PET-MRI

Behavioral:
• Patient-Reported Outcomes
For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
German Society for Pediatric Oncology and Hematology GPOH gGmbH	Deutsche Krebshilfe e.V., Bonn (Germany)

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate after induction therapy	Complete response by MRI and PET will be determined as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria	MRI and PET will be done 17-22 days after start of induction therapy cycle 3 (each cycle is 21 days)
Secondary	Overall and Event-free Survival	Overall and event-free survival rates will be analysed with suitable descriptive methods (Kaplan Meyer estimates with confidence intervals) and compared with historical data using descriptive log-rank tests	2 years after study enrolment
Secondary	Number of Treatment-Related Adverse Events	Adverse events will be classified using the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) version 5.0 by investigator assessment. Descriptive methods (frequency tables, rates of AE's and SAE's with 95% confidence intervals) will be applied	At day 0 of chemotherapy cycles 1, 2 and 3, each; at day 20-25 after beginning of chemotherapy cycle 3 (each cycle is 21 days); within 2-3 weeks after the last dose of radiotherapy; 100 days following the last dose of Nivolumab
Secondary	Efficacy based on PD-L1 expression in tumor tissue	PD-L1-stained % of tumor cells at the time of diagnosis will be associated to the rate of response after induction therapy and EFS and OS	Response to induction therapy will be measured 17-22 days after start of induction therapy cycle 3 (each cycle is 21 days), event-free and overall survival will be determined 2 years after study enrolment