Nivolumab in Children and Adults With Nasopharyngeal Carcinoma

NCT06019130 | Recruiting Phase 2 DMC

• 1 other identifier: EUCT: 2022-500676-59-00
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 31

Brief 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.

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Cancer; Nasopharyngeal Neoplasms; Nasopharynx Cancer

Keywords

Immunotherapy; Nivolumab; Children; Adults; Chemotherapy; Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall and Event-free Survival

  2 years after study enrolment

• Number of Treatment-Related Adverse Events

  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

• Efficacy based on PD-L1 expression in tumor tissue

  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

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Cisplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Drug: Interferon beta-1a; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes

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

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Cisplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Drug: Interferon beta-1a; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes

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

EXPERIMENTAL

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).

Drug: Nivolumab; Drug: Cisplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes

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

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Cisplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes

Patients > 25 years with metastatic disease at diagnosis

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Cisplatin; Drug: Gemcitabine; Radiation: Radiotherapy; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes

Interventions

Nivolumab DRUG

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

Also known as: Opdivo

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Cisplatin DRUG

Cisplatin during induction chemotherapy and during radiochemotherapy in all groups

Also known as: Cisplatin Teva

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

5-Fluorouracil DRUG

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

Also known as: Fluorouracil-GRY

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Gemcitabine DRUG

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

Also known as: Gemcitabin-GRY

Patients > 25 years with metastatic disease at diagnosis

Radiotherapy RADIATION

After induction therapy in all patients

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Interferon beta-1a DRUG

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

Also known as: Rebif

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy

MRI PROCEDURE

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

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

PET PROCEDURE

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

Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Patient-Reported Outcomes 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; Patients < 26 years with non-metastatic disease with CR or PR after induction therapy; Patients > 25 years with metastatic disease at diagnosis; Patients > 25 years with non-metastatic disease with SD or PD after induction therapy; Patients >25 years with non-metastatic disease with CR or PR after induction therapy

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Stage II or higher in patients ≤ 25 years of age, stage III and IV in patients \> 25 years of age (AJCC, 8th edition)
• Measurable disease by MRI per RECIST 1.1 criteria
• 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
• Written informed consent by legal guardians (if patient not ≥ 18 years) and patient prior to study participation

You may not qualify if:

• Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II in patients \> 25 years of age
• Recurrent nasopharyngeal carcinoma
• Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
• Prior chemotherapy and/or radiotherapy
• Other active malignancy
• 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.
• Subjects who are enrolled in another clinical trial
• Subjects with prior organ allograft or allogenic bone marrow transplantation
• 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.
• 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.
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Inadequate hematologic, renal or hepatic function defined by any of the following screening laboratory values:
• WBC \< 2 000/µl
• Neutrophils \< 1 500/µl

Sponsors & Collaborators

• German Society for Pediatric Oncology and Hematology GPOH gGmbH: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator

Study Sites (31)

Uniklinik RWTH Aachen, Department of Internal Medicine

Aachen, 52074, Germany

RECRUITING

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

Aachen, 52074, Germany

ACTIVE NOT RECRUITING

Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin

Berlin, 13353, Germany

ACTIVE NOT RECRUITING

Evangelisches Klinikum Bethel, Children's Hospital

Bielefeld, 33617, Germany

ACTIVE NOT RECRUITING

Department of Pediatric Hematology and Oncology, University Hospital

Bonn, 53127, Germany

NOT YET RECRUITING

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

Cologne, 50937, Germany

RECRUITING

Children's Hospital, Carl-Thiem Klinikum Cottbus

Cottbus, 03048, Germany

RECRUITING

Clinic for Children and Adolescent Medicine, Klinikum Dortmund

Dortmund, 44145, Germany

ACTIVE NOT RECRUITING

Department of Internal Medicine, Klinikum Dortmund

Dortmund, 44145, Germany

ACTIVE NOT RECRUITING

Department of Pediatrics, University Hospital, Technische Universität Dresden

Dresden, 01307, Germany

ACTIVE NOT RECRUITING

Department fo Radiotherapy, University Hospital

Erlangen, 91054, Germany

RECRUITING

Department of Pediatrics, University Hospital Erlangen

Erlangen, 91054, Germany

ACTIVE NOT RECRUITING

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

Essen, 45147, Germany

NOT YET RECRUITING

Department of Pediatric Hematology and Oncology, University Hospital Essen

Essen, 45147, Germany

NOT YET RECRUITING

Department of Pediatrics, University Hospital

Frankfurt, 60590, Germany

NOT YET RECRUITING

Department of Pediatric Hematology/Oncology, University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

NOT YET RECRUITING

Department of Pediatric Oncology, Justus-Liebig University of Giessen

Giessen, 35392, Germany

ACTIVE NOT RECRUITING

Department of Pediatric Oncology, University Hospital

Göttingen, 37075, Germany

NOT YET RECRUITING

Department of Pediatric Hematology/Oncology, University Medicine Greifswald

Greifswald, 17475, Germany

NOT YET RECRUITING

Universitätsklinikum Halle, Klinik für Pädiatrie I

Halle, 06120, Germany

RECRUITING

Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf,

Hamburg, 20246, Germany

RECRUITING

Department of Pediatric Oncology, University Children's Hospital

Hamburg, Germany

RECRUITING

Department of Otorhinolaryngology, Jena University Hospital

Jena, 07743, Germany

ACTIVE NOT RECRUITING

Department of Pediatric Oncology, University Hospital Kiel

Kiel, 24105, Germany

RECRUITING

Department of Pediatrics, University Hospital Mageburg

Magdeburg, 39120, Germany

NOT YET RECRUITING

Pediatric Hematology/Oncology, University Medicine Mainz

Mainz, 55131, Germany

ACTIVE NOT RECRUITING

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

Mannheim, 68167, Germany

RECRUITING

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

Münster, 48149, Germany

ACTIVE NOT RECRUITING

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

Regensburg, 93053, Germany

NOT YET RECRUITING

Universitätsklinikum Tübingen, Klinik für Pädiatrie I

Tübingen, 72076, Germany

RECRUITING

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

Würzburg, 97080, Germany

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Interventions

Nivolumab; Cisplatin; Fluorouracil; Gemcitabine; Radiotherapy; Interferon beta-1a; Patient Reported Outcome Measures

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Therapeutics; Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Health Care Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Services Research; Health Planning; Health Care Economics and Organizations; Patient Outcome Assessment; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Study Officials

• Udo Kontny, MD

  Uniklinik RWTH Aachen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helena Kerp, PhD

CONTACT

+49 201 74 94 96 14; h.kerp@forschung-paediatrie.de

Tristan Römer, MD.

CONTACT

+49 241 80 38063; troemer@ukaachen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Div. Pediatric Hematology, Oncology, Stem Cell Transplantation

Model Details: A phase-II optimum Simon design with alpha=0.1 and beta=0.2 will be used.

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: August 31, 2023
• Study Start: January 10, 2023
• Primary Completion: January 9, 2026
• Study Completion (Estimated): January 9, 2028
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (31)