Trial Title:
Nivolumab in Children and Adults With Nasopharyngeal Carcinoma
NCT ID:
NCT06019130
Condition:
Nasopharyngeal Carcinoma
Nasopharyngeal Cancer
Nasopharyngeal Neoplasms
Nasopharynx Cancer
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms
Interferons
Interferon-beta
Interferon beta-1a
Cisplatin
Gemcitabine
Nivolumab
Fluorouracil
Conditions: Keywords:
Immunotherapy
Nivolumab
Children
Adults
Chemotherapy
Immune Checkpoint Inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A phase-II optimum Simon design with alpha=0.1 and beta=0.2 will be used.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in
patients with SD or PD after induction or metastases
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin during induction chemotherapy and during radiochemotherapy in all groups
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Other name:
Cisplatin Teva
Intervention type:
Drug
Intervention name:
5-Fluorouracil
Description:
5-Fluoruracil during induction chemotherapy in all groups except of adults > 25 years
with metastatic disease at diagnosis
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Other name:
Fluorouracil-GRY
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine during induction chemotherapy in patients > 25 years with metastatic disease
at diagnosis
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Other name:
Gemcitabin-GRY
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
After induction therapy in all patients
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Intervention type:
Drug
Intervention name:
Interferon beta-1a
Description:
In patients < 26 years after end of radiochemotherapy for 6 months
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Other name:
Rebif
Intervention type:
Procedure
Intervention name:
MRI
Description:
At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Intervention type:
Procedure
Intervention name:
PET
Description:
At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy,
either as PET-CT or PET-MRI
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
Intervention type:
Behavioral
Intervention name:
Patient-Reported Outcomes
Description:
For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after
enrolment
Arm group label:
Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases
Arm group label:
Patients < 26 years with non-metastatic disease with CR or PR after induction therapy
Arm group label:
Patients > 25 years with metastatic disease at diagnosis
Arm group label:
Patients > 25 years with non-metastatic disease with SD or PD after induction therapy
Arm group label:
Patients >25 years with non-metastatic disease with CR or PR after induction therapy
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.
Detailed 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.
Criteria for 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.
Gender:
All
Minimum age:
3 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Uniklinik RWTH Aachen, Department of Internal Medicine
Address:
City:
Aachen
Zip:
52074
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Mareike Tometten, MD
Phone:
0241-80-80703
Email:
mtometten@ukaachen.de
Facility:
Name:
Uniklinik RWTH Aachen, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation
Address:
City:
Aachen
Zip:
52074
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin
Address:
City:
Berlin
Zip:
13353
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Evangelisches Klinikum Bethel, Children's Hospital
Address:
City:
Bielefeld
Zip:
33617
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatric Hematology and Oncology, University Hospital
Address:
City:
Bonn
Zip:
53127
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Dagmar Dilloo, MD
Phone:
+49-228-287-33215
Email:
dagmar.dilloo@ukbonn.de
Facility:
Name:
Children's Hospital, Carl-Thiem Klinikum Cottbus
Address:
City:
Cottbus
Zip:
03048
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Georg Schwabe, MD
Phone:
+49-355-46-2336
Email:
G.Schwabe@ctk.de
Facility:
Name:
Clinic for Children and Adolescent Medicine, Klinikum Dortmund
Address:
City:
Dortmund
Zip:
44145
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Internal Medicine, Klinikum Dortmund
Address:
City:
Dortmund
Zip:
44145
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatrics, University Hospital, Technische Universität Dresden
Address:
City:
Dresden
Zip:
01307
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department fo Radiotherapy, University Hospital
Address:
City:
Erlangen
Zip:
91054
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Marlen Haderlein, MD
Phone:
+49-9131-8533405
Email:
st-studiensekretariat@uk-erlangen.de
Facility:
Name:
Department of Pediatrics, University Hospital Erlangen
Address:
City:
Erlangen
Zip:
91054
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Stefan Kasper-Virchow, MD
Phone:
+49-201-72384150
Email:
WTZI-Studie@uk-essen.de
Facility:
Name:
Department of Pediatric Hematology and Oncology, University Hospital Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Stefan Schönberger, MD
Phone:
+49-201-723-85190.
Email:
Stefan.Schoenberger@uk-essen.de
Facility:
Name:
Department of Pediatrics, University Hospital
Address:
City:
Frankfurt
Zip:
60590
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Konrad Bochennek, MD
Phone:
+49-69-6301-4157
Email:
Konrad.Bochennek@kgu.de
Facility:
Name:
Department of Pediatric Hematology/Oncology, University Hospital Freiburg
Address:
City:
Freiburg
Zip:
79106
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Simone Hettmer, MD
Phone:
+49-761-270-46940
Email:
simone.hettmer@uniklinik-freiburg.de
Facility:
Name:
Department of Pediatric Oncology, Justus-Liebig University of Giessen
Address:
City:
Giessen
Zip:
35392
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatric Hematology/Oncology, University Medicine Greifswald
Address:
City:
Greifswald
Zip:
17475
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Karoline Ehlert, MD
Phone:
+49-3834-866325
Email:
karoline.ehlert@med.uni-greifswald.de
Facility:
Name:
Department of Pediatric Oncology, University Hospital
Address:
City:
Göttingen
Zip:
37075
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Christof Kramm, MD
Phone:
+49-551-39-63081
Email:
paedonko@med.uni-goettingen.de
Facility:
Name:
Universitätsklinikum Halle, Klinik für Pädiatrie I
Address:
City:
Halle
Zip:
06120
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Jessica Höll, MD
Phone:
+49-345-557-2388
Email:
Jessica.Hoell@uk-halle.de
Facility:
Name:
Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf,
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Henrike Zech, MD
Phone:
+49-407-410-52364
Email:
hzech@uke.de
Facility:
Name:
Department of Pediatric Oncology, University Children's Hospital
Address:
City:
Hamburg
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Uwe Kordes, MD
Phone:
+49-40-7410-53796
Email:
u.kordes@uke.de
Facility:
Name:
Department of Otorhinolaryngology, Jena University Hospital
Address:
City:
Jena
Zip:
07743
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatric Oncology, University Hospital Kiel
Address:
City:
Kiel
Zip:
24105
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Simon Vieth, MD
Phone:
+49-431-500-20119
Email:
Simon.Vieth@uksh.de
Facility:
Name:
Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Jens Klußmann, MD
Phone:
+49-221-4784750
Email:
jens.klussmann@uk-koeln.de
Facility:
Name:
Department of Pediatrics, University Hospital Mageburg
Address:
City:
Magdeburg
Zip:
39120
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Antje Redlich, MD
Phone:
+49-391-67-24235
Email:
Antje.Redlich@med.ovgu.de
Facility:
Name:
Pediatric Hematology/Oncology, University Medicine Mainz
Address:
City:
Mainz
Zip:
55131
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim,
Address:
City:
Mannheim
Zip:
68167
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Annette Affolter, MD
Phone:
+49-621-383-3965
Email:
annette.affolter@umm.de
Facility:
Name:
Department of Pediatric Hematology and Oncology, University Children's Hospital
Address:
City:
Münster
Zip:
48149
Country:
Germany
Status:
Active, not recruiting
Facility:
Name:
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital
Address:
City:
Regensburg
Zip:
93053
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Marcus Jakob, MD
Phone:
+49-941-944-2101
Email:
Marcus.Jakob@klinik.uni-regensburg.de
Facility:
Name:
Universitätsklinikum Tübingen, Klinik für Pädiatrie I
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Ines Brecht, MD
Phone:
+49-7071-29-83773
Email:
Ines.Brecht@med.uni-tuebingen.de
Facility:
Name:
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, University of Würzburg
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Active, not recruiting
Start date:
January 10, 2023
Completion date:
January 9, 2028
Lead sponsor:
Agency:
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Agency class:
Other
Collaborator:
Agency:
Deutsche Krebshilfe e.V., Bonn (Germany)
Agency class:
Other
Source:
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06019130
