Nivolumab in Children and Adults With Nasopharyngeal Carcinoma

NCT ID: NCT06019130

Last Updated: 2024-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-10

Study Completion Date

2028-01-09

Brief Summary

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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

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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.

Conditions

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Nasopharyngeal Carcinoma Nasopharyngeal Cancer Nasopharyngeal Neoplasms Nasopharynx Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

A phase-II optimum Simon design with alpha=0.1 and beta=0.2 will be used.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Patients < 26 years with non-metastatic disease with CR or PR after induction therapy

Participants receive Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) during induction chemotherapy for a total of 3 doses, starting on day 1 of cycle 1 of induction standard chemotherapy with cisplatin 100 mg/m2 on day 1, plus 5-fluorouracil 1,000 mg/m2/d from day 1-5.

After induction therapy patients will undergo standard radiochemotherapy. Primary PTV1 including elective irradiated LN-levels, will be 45Gy, with a boost ad 59.4Gy in patients with PR or a reduced boost at 54Gy in patients with CR. Cisplatin will be administered at 3x20mg/m2 in the first and last week of radiotherapy, each.

Radiochemotherapy is followed by maintenance therapy with recombinant interferon-ß1a at 3x6Mio IU/week s.c. for 6 months.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Cisplatin

Intervention Type DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

5-Fluorouracil

Intervention Type DRUG

5-Fluoruracil during induction chemotherapy in all groups except of adults \> 25 years with metastatic disease at diagnosis

Radiotherapy

Intervention Type RADIATION

After induction therapy in all patients

Interferon beta-1a

Intervention Type DRUG

In patients \< 26 years after end of radiochemotherapy for 6 months

MRI

Intervention Type PROCEDURE

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

PET

Intervention Type PROCEDURE

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

Patient-Reported Outcomes

Intervention Type BEHAVIORAL

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases

Participants receive Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) during induction chemotherapy for a total of 3 doses, starting on day 1 of cycle 1 of induction standard chemotherapy with cisplatin 100 mg/m2 on day 1, plus 5-fluorouracil 1,000 mg/m2/d from day 1-5. Patients with metastases responding to induction therapy may have a fourth cycle of induction therapy, including a fourth dose of Nivolumab.

After induction therapy patients will undergo standard radiochemotherapy. Primary PTV1 including elective irradiated LN-levels, will be 45Gy, with a boost ad 59.4Gy. Cisplatin will be administered at 3x20mg/m2 in the first and last week of radiotherapy, each. Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) will be continued during radiochemotherapy, adding a total of 3 further doses of Nivolumab.

Radiochemotherapy is followed by maintenance therapy with recombinant interferon-ß1a at 3x6Mio IU/week s.c. for 6 months.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Cisplatin

Intervention Type DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

5-Fluorouracil

Intervention Type DRUG

5-Fluoruracil during induction chemotherapy in all groups except of adults \> 25 years with metastatic disease at diagnosis

Radiotherapy

Intervention Type RADIATION

After induction therapy in all patients

Interferon beta-1a

Intervention Type DRUG

In patients \< 26 years after end of radiochemotherapy for 6 months

MRI

Intervention Type PROCEDURE

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

PET

Intervention Type PROCEDURE

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

Patient-Reported Outcomes

Intervention Type BEHAVIORAL

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Participants receive Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) during induction chemotherapy for a total of 3 doses, starting on day 1 of cycle 1 of induction standard chemotherapy with cisplatin 100 mg/m2 on day 1, plus 5-fluorouracil 1,000 mg/m2/d from day 1-5.

After induction therapy patients will undergo standard radiochemotherapy as outlined in current international guidelines (e.g. NCCN, ESMO).

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Cisplatin

Intervention Type DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

5-Fluorouracil

Intervention Type DRUG

5-Fluoruracil during induction chemotherapy in all groups except of adults \> 25 years with metastatic disease at diagnosis

Radiotherapy

Intervention Type RADIATION

After induction therapy in all patients

MRI

Intervention Type PROCEDURE

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

PET

Intervention Type PROCEDURE

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

Patient-Reported Outcomes

Intervention Type BEHAVIORAL

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Patients > 25 years with non-metastatic disease with SD or PD after induction therapy

Participants receive Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) during induction chemotherapy for a total of 3 doses, starting on day 1 of cycle 1 of induction standard chemotherapy with cisplatin 100 mg/m2 on day 1, plus 5-fluorouracil 1,000 mg/m2/d from day 1-5.

After induction therapy patients will undergo standard radiochemotherapy as outlined in current international guidelines (e.g. NCCN, ESMO). Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) will be continued during radiochemotherapy, adding a total of 3 further doses of Nivolumab.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Cisplatin

Intervention Type DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

5-Fluorouracil

Intervention Type DRUG

5-Fluoruracil during induction chemotherapy in all groups except of adults \> 25 years with metastatic disease at diagnosis

Radiotherapy

Intervention Type RADIATION

After induction therapy in all patients

MRI

Intervention Type PROCEDURE

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

PET

Intervention Type PROCEDURE

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

Patient-Reported Outcomes

Intervention Type BEHAVIORAL

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Patients > 25 years with metastatic disease at diagnosis

Participants receive Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) during induction chemotherapy for a total of 3 doses, starting on day 1 of cycle 1 of induction standard chemotherapy with cisplatin 80 mg/m2 on day 1, plus gemcitabine 1,000 mg/m2/d on day 1 and day 8, respectively. Patients responding to induction therapy may have a fourth cycle of induction therapy, including a fourth dose of Nivolumab.

After induction therapy patients will undergo standard radiochemotherapy as outlined in current international guidelines (e.g. NCCN, ESMO). Nivolumab (4.5 mg/kg BW (max. 360 mg) every three weeks) will be continued during radiochemotherapy, adding a total of 3 further doses of Nivolumab.

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Cisplatin

Intervention Type DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

Gemcitabine

Intervention Type DRUG

Gemcitabine during induction chemotherapy in patients \> 25 years with metastatic disease at diagnosis

Radiotherapy

Intervention Type RADIATION

After induction therapy in all patients

MRI

Intervention Type PROCEDURE

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

PET

Intervention Type PROCEDURE

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

Patient-Reported Outcomes

Intervention Type BEHAVIORAL

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Interventions

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Nivolumab

Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases

Intervention Type DRUG

Cisplatin

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

Intervention Type DRUG

5-Fluorouracil

5-Fluoruracil during induction chemotherapy in all groups except of adults \> 25 years with metastatic disease at diagnosis

Intervention Type DRUG

Gemcitabine

Gemcitabine during induction chemotherapy in patients \> 25 years with metastatic disease at diagnosis

Intervention Type DRUG

Radiotherapy

After induction therapy in all patients

Intervention Type RADIATION

Interferon beta-1a

In patients \< 26 years after end of radiochemotherapy for 6 months

Intervention Type DRUG

MRI

At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy

Intervention Type PROCEDURE

PET

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

Intervention Type PROCEDURE

Patient-Reported Outcomes

For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment

Intervention Type BEHAVIORAL

Other Intervention Names

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Opdivo Cisplatin Teva Fluorouracil-GRY Gemcitabin-GRY Rebif

Eligibility Criteria

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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.
Minimum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Deutsche Krebshilfe e.V., Bonn (Germany)

OTHER

Sponsor Role collaborator

German Society for Pediatric Oncology and Hematology GPOH gGmbH

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Udo Kontny

Head, Div. Pediatric Hematology, Oncology, Stem Cell Transplantation

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Udo Kontny, MD

Role: PRINCIPAL_INVESTIGATOR

Uniklinik RWTH Aachen

Locations

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Uniklinik RWTH Aachen, Department of Internal Medicine

Aachen, , Germany

Site Status RECRUITING

Uniklinik RWTH Aachen, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation

Aachen, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin

Berlin, , Germany

Site Status ACTIVE_NOT_RECRUITING

Evangelisches Klinikum Bethel, Children's Hospital

Bielefeld, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatric Hematology and Oncology, University Hospital

Bonn, , Germany

Site Status NOT_YET_RECRUITING

Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne

Cologne, , Germany

Site Status RECRUITING

Children's Hospital, Carl-Thiem Klinikum Cottbus

Cottbus, , Germany

Site Status RECRUITING

Clinic for Children and Adolescent Medicine, Klinikum Dortmund

Dortmund, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Internal Medicine, Klinikum Dortmund

Dortmund, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatrics, University Hospital, Technische Universität Dresden

Dresden, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department fo Radiotherapy, University Hospital

Erlangen, , Germany

Site Status RECRUITING

Department of Pediatrics, University Hospital Erlangen

Erlangen, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Medical Oncology, West German Cancer Center, University Hospital Essen

Essen, , Germany

Site Status NOT_YET_RECRUITING

Department of Pediatric Hematology and Oncology, University Hospital Essen

Essen, , Germany

Site Status NOT_YET_RECRUITING

Department of Pediatrics, University Hospital

Frankfurt, , Germany

Site Status NOT_YET_RECRUITING

Department of Pediatric Hematology/Oncology, University Hospital Freiburg

Freiburg im Breisgau, , Germany

Site Status NOT_YET_RECRUITING

Department of Pediatric Oncology, Justus-Liebig University of Giessen

Giessen, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatric Oncology, University Hospital

Göttingen, , Germany

Site Status NOT_YET_RECRUITING

Department of Pediatric Hematology/Oncology, University Medicine Greifswald

Greifswald, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Halle, Klinik für Pädiatrie I

Halle, , Germany

Site Status RECRUITING

Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf,

Hamburg, , Germany

Site Status RECRUITING

Department of Pediatric Oncology, University Children's Hospital

Hamburg, , Germany

Site Status RECRUITING

Department of Otorhinolaryngology, Jena University Hospital

Jena, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatric Oncology, University Hospital Kiel

Kiel, , Germany

Site Status RECRUITING

Department of Pediatrics, University Hospital Mageburg

Magdeburg, , Germany

Site Status NOT_YET_RECRUITING

Pediatric Hematology/Oncology, University Medicine Mainz

Mainz, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim,

Mannheim, , Germany

Site Status RECRUITING

Department of Pediatric Hematology and Oncology, University Children's Hospital

Münster, , Germany

Site Status ACTIVE_NOT_RECRUITING

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital

Regensburg, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Tübingen, Klinik für Pädiatrie I

Tübingen, , Germany

Site Status RECRUITING

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, University of Würzburg

Würzburg, , Germany

Site Status ACTIVE_NOT_RECRUITING

Countries

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Germany

Central Contacts

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Helena Kerp, PhD

Role: CONTACT

+49 201 74 94 96 14

Tristan Römer, MD.

Role: CONTACT

+49 241 80 38063

Facility Contacts

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Mareike Tometten, MD

Role: primary

0241-80-80703

Dagmar Dilloo, MD

Role: primary

+49-228-287-33215

Jens Klußmann, MD

Role: primary

+49-221-4784750

Georg Schwabe, MD

Role: primary

+49-355-46-2336

Marlen Haderlein, MD

Role: primary

+49-9131-8533405

Stefan Kasper-Virchow, MD

Role: primary

+49-201-72384150

Stefan Schönberger, MD

Role: primary

+49-201-723-85190.

Konrad Bochennek, MD

Role: primary

+49-69-6301-4157

Simone Hettmer, MD

Role: primary

+49-761-270-46940

Christof Kramm, MD

Role: primary

+49-551-39-63081

Karoline Ehlert, MD

Role: primary

+49-3834-866325

Jessica Höll, MD

Role: primary

+49-345-557-2388

Henrike Zech, MD

Role: primary

+49-407-410-52364

Uwe Kordes, MD

Role: primary

+49-40-7410-53796

Simon Vieth, MD

Role: primary

+49-431-500-20119

Antje Redlich, MD

Role: primary

+49-391-67-24235

Annette Affolter, MD

Role: primary

+49-621-383-3965

Marcus Jakob, MD

Role: primary

+49-941-944-2101

Ines Brecht, MD

Role: primary

+49-7071-29-83773

Other Identifiers

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EUCT: 2022-500676-59-00

Identifier Type: -

Identifier Source: org_study_id

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