Nasopharyngeal CarcinomaPhase 2NPC-NivoNCT06019130
Nivolumab in Children and Adults With Nasopharyngeal Carcinoma
A Phase 2 study testing Nivolumab, Cisplatin and 5-Fluorouracil in people with Nasopharyngeal Carcinoma and Nasopharyngeal Cancer, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 31 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Nasopharyngeal Carcinoma, Nasopharyngeal Cancer, Nasopharyngeal Neoplasms
- What is being tested?
- Nivolumab, Cisplatin and 5-Fluorouracil
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 31 sitesGermany
- Study dates
- 10 Jan 2023to 9 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- The subject received an investigational drug within 30 days prior to inclusion into this study
- 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
- Platelets < 100 x 10e3/µL
- Hemoglobin < 9.0 g/dL
- Creatinine >1.5 x ULN or creatinine clearance < 50 mL/min (using the Cockcroft Gault formula or Schwartz formula in patients < 18 years)
- AST/ALT > 3 x ULN (> 5 x ULN if liver metastases)
- Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level ≥ 3.0 x ULN)
- Hearing loss > 20 dB loss at 3 kHz due to an inner ear disorder and not caused by tumour burden
- History of allergy or hypersensitivity to platinum-containing compounds or other study drug components
- 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).
- Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug.
- Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lansky score ≥ 60 (age < 16).
- 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.
- 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.
- 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)
- Lactating females
- Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
- The subject is unwilling or unable to follow the procedures outlined in the protocol
- The subject is mentally or legally incapacitated.
Trial locations and contacts
31 sites in 1 country. Contact the study team or a site near you to ask about taking part.
31 sites in 1 country
Germany31 sites, 19 recruiting
- Recruiting
Uniklinik RWTH Aachen, Department of Internal Medicine
Aachen, 52074
Mareike Tometten, MD, 0241-80-80703, mtometten@ukaachen.de
- Active, not recruiting
Uniklinik RWTH Aachen, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation
Aachen, 52074
- Active, not recruiting
Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin
Berlin, 13353
- Active, not recruiting
Evangelisches Klinikum Bethel, Children's Hospital
Bielefeld, 33617
- Not yet recruiting
Department of Pediatric Hematology and Oncology, University Hospital
Bonn, 53127
Dagmar Dilloo, MD, +49-228-287-33215, dagmar.dilloo@ukbonn.de
- Recruiting
Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne
Cologne, 50937
Jens Klußmann, MD, +49-221-4784750, jens.klussmann@uk-koeln.de
- Recruiting
Children's Hospital, Carl-Thiem Klinikum Cottbus
Cottbus, 03048
Georg Schwabe, MD, +49-355-46-2336, G.Schwabe@ctk.de
- Active, not recruiting
Clinic for Children and Adolescent Medicine, Klinikum Dortmund
Dortmund, 44145
- Active, not recruiting
Department of Internal Medicine, Klinikum Dortmund
Dortmund, 44145
- Active, not recruiting
Department of Pediatrics, University Hospital, Technische Universität Dresden
Dresden, 01307
- Recruiting
Department fo Radiotherapy, University Hospital
Erlangen, 91054
Marlen Haderlein, MD, +49-9131-8533405, st-studiensekretariat@uk-erlangen.de
- Active, not recruiting
Department of Pediatrics, University Hospital Erlangen
Erlangen, 91054
- Not yet recruiting
Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Essen, 45147
Stefan Kasper-Virchow, MD, +49-201-72384150, WTZI-Studie@uk-essen.de
- Not yet recruiting
Department of Pediatric Hematology and Oncology, University Hospital Essen
Essen, 45147
Stefan Schönberger, MD, +49-201-723-85190., Stefan.Schoenberger@uk-essen.de
- Not yet recruiting
Department of Pediatrics, University Hospital
Frankfurt, 60590
Konrad Bochennek, MD, +49-69-6301-4157, Konrad.Bochennek@kgu.de
- Not yet recruiting
Department of Pediatric Hematology/Oncology, University Hospital Freiburg
Freiburg im Breisgau, 79106
Simone Hettmer, MD, +49-761-270-46940, simone.hettmer@uniklinik-freiburg.de
- Active, not recruiting
Department of Pediatric Oncology, Justus-Liebig University of Giessen
Giessen, 35392
- Not yet recruiting
Department of Pediatric Oncology, University Hospital
Göttingen, 37075
Christof Kramm, MD, +49-551-39-63081, paedonko@med.uni-goettingen.de
- Not yet recruiting
Department of Pediatric Hematology/Oncology, University Medicine Greifswald
Greifswald, 17475
Karoline Ehlert, MD, +49-3834-866325, karoline.ehlert@med.uni-greifswald.de
- Recruiting
Universitätsklinikum Halle, Klinik für Pädiatrie I
Halle, 06120
Jessica Höll, MD, +49-345-557-2388, Jessica.Hoell@uk-halle.de
- Recruiting
Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf,
Hamburg, 20246
Henrike Zech, MD, +49-407-410-52364, hzech@uke.de
- Recruiting
Department of Pediatric Oncology, University Children's Hospital
Hamburg
Uwe Kordes, MD, +49-40-7410-53796, u.kordes@uke.de
- Active, not recruiting
Department of Otorhinolaryngology, Jena University Hospital
Jena, 07743
- Recruiting
Department of Pediatric Oncology, University Hospital Kiel
Kiel, 24105
Simon Vieth, MD, +49-431-500-20119, Simon.Vieth@uksh.de
- Not yet recruiting
Department of Pediatrics, University Hospital Mageburg
Magdeburg, 39120
Antje Redlich, MD, +49-391-67-24235, Antje.Redlich@med.ovgu.de
- Active, not recruiting
Pediatric Hematology/Oncology, University Medicine Mainz
Mainz, 55131
- Recruiting
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim,
Mannheim, 68167
Annette Affolter, MD, +49-621-383-3965, annette.affolter@umm.de
- Active, not recruiting
Department of Pediatric Hematology and Oncology, University Children's Hospital
Münster, 48149
- Not yet recruiting
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital
Regensburg, 93053
Marcus Jakob, MD, +49-941-944-2101, Marcus.Jakob@klinik.uni-regensburg.de
- Recruiting
Universitätsklinikum Tübingen, Klinik für Pädiatrie I
Tübingen, 72076
Ines Brecht, MD, +49-7071-29-83773, Ines.Brecht@med.uni-tuebingen.de
- Active, not recruiting
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, University of Würzburg
Würzburg, 97080
About this study
Official title: Nivolumab in Combination With Cisplatin and 5-Fluorouracil as Induction Therapy in Children and Adults With EBV-positive Nasopharyngeal Carcinoma
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.
Read the 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.
- Conditions
- Nasopharyngeal Carcinoma, Nasopharyngeal Cancer, Nasopharyngeal Neoplasms, Nasopharynx Cancer
- Being tested
- Nivolumab, Cisplatin, 5-Fluorouracil, Gemcitabine, Radiotherapy
- Keywords
- Immunotherapy, Nivolumab, Children, Adults, Chemotherapy, Immune Checkpoint Inhibitor
- Medical subject headings
- Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases
CisplatinDrug
Also called Cisplatin Teva
Cisplatin during induction chemotherapy and during radiochemotherapy in all groups
5-FluorouracilDrug
Also called Fluorouracil-GRY
5-Fluoruracil during induction chemotherapy in all groups except of adults > 25 years with metastatic disease at diagnosis
GemcitabineDrug
Also called Gemcitabin-GRY
Gemcitabine during induction chemotherapy in patients > 25 years with metastatic disease at diagnosis
RadiotherapyRadiation
After induction therapy in all patients
Interferon beta-1aDrug
Also called Rebif
In patients < 26 years after end of radiochemotherapy for 6 months
MRIProcedure or surgery
At diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy
PETProcedure or surgery
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 OutcomesBehavioural
For all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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). Receives: 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. Receives: 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. Receives: Drug: Nivolumab; Drug: Cisplatin; Drug: Gemcitabine; Radiation: Radiotherapy; Procedure: MRI; Procedure: PET; Behavioral: Patient-Reported Outcomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
Measured: 2 years after study enrolment
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
Measured: 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
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2023
- Study start10 Jan 2023
- Primary completion9 Jan 2026 (estimated)
- Study completion9 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A phase-II optimum Simon design with alpha=0.1 and beta=0.2 will be used.
- Masking
- None (open label)
- Enrolment
- 57 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Society for Pediatric Oncology and Hematology GPOH gGmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany)
- Responsible party
- Principal investigator, Prof. Dr. Udo Kontny, RWTH Aachen University
- Investigators
- Udo Kontny, MD, Principal investigator, Uniklinik RWTH Aachen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06019130
- Sponsor's protocol ID
- EUCT: 2022-500676-59-00
- Acronym
- NPC-Nivo
- Status last verified
- May 2024
- First submitted
- 15 Aug 2023
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nivolumab in Combination With Cisplatin and 5-Fluorouracil as Induction Therapy in Children and Adults With EBV-positive Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT06019130
- Acronym / sponsor ID
- NPC-Nivo / EUCT: 2022-500676-59-00
- Conditions
- Nasopharyngeal Carcinoma, Nasopharyngeal Cancer, Nasopharyngeal Neoplasms, Nasopharynx Cancer
- Keywords
- Immunotherapy, Nivolumab, Children, Adults, Chemotherapy, Immune Checkpoint Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 57 participants (estimated)
- Lead sponsor
- German Society for Pediatric Oncology and Hematology GPOH gGmbHUniversity, hospital or other
- Collaborators
- Deutsche Krebshilfe e.V., Bonn (Germany)
- Study start
- 10 Jan 2023 (actual)
- Primary completion
- 9 Jan 2026 (estimated)
- Study completion
- 9 Jan 2028 (estimated)
- First posted
- 31 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- A phase-II optimum Simon design with alpha=0.1 and beta=0.2 will be used.
| Arm | Type | Receives |
|---|---|---|
| Patients < 26 years with non-metastatic disease with CR or PR after induction therapy | Experimental | Drug: Nivolumab, Drug: Cisplatin, Drug: 5-Fluorouracil, Radiation: Radiotherapy, Drug: Interferon beta-1a, Procedure: MRI, Procedure: PET, Behavioral: Patient-Reported OutcomesParticipants 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. |
| Patients < 26 y with no metastases and SD or PD after induction therapy or patients with metastases | Experimental | Drug: Nivolumab, Drug: Cisplatin, Drug: 5-Fluorouracil, Radiation: Radiotherapy, Drug: Interferon beta-1a, Procedure: MRI, Procedure: PET, Behavioral: Patient-Reported OutcomesParticipants 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. |
| Patients >25 years with non-metastatic disease with CR or PR after induction therapy | Experimental | Drug: Nivolumab, Drug: Cisplatin, Drug: 5-Fluorouracil, Radiation: Radiotherapy, Procedure: MRI, Procedure: PET, Behavioral: Patient-Reported OutcomesParticipants 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). |
| Patients > 25 years with non-metastatic disease with SD or PD after induction therapy | Experimental | Drug: Nivolumab, Drug: Cisplatin, Drug: 5-Fluorouracil, Radiation: Radiotherapy, Procedure: MRI, Procedure: PET, Behavioral: Patient-Reported OutcomesParticipants 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. |
| Patients > 25 years with metastatic disease at diagnosis | Experimental | Drug: Nivolumab, Drug: Cisplatin, Drug: Gemcitabine, Radiation: Radiotherapy, Procedure: MRI, Procedure: PET, Behavioral: Patient-Reported OutcomesParticipants 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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab during induction chemotherapy in all groups and during radiochemotherapy in patients with SD or PD after induction or metastases | Drug | 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 |
| CisplatinAlso: Cisplatin TevaCisplatin during induction chemotherapy and during radiochemotherapy in all groups | Drug | 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-FluorouracilAlso: Fluorouracil-GRY5-Fluoruracil during induction chemotherapy in all groups except of adults > 25 years with metastatic disease at diagnosis | Drug | 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 |
| GemcitabineAlso: Gemcitabin-GRYGemcitabine during induction chemotherapy in patients > 25 years with metastatic disease at diagnosis | Drug | Patients > 25 years with metastatic disease at diagnosis |
| RadiotherapyAfter induction therapy in all patients | Radiation | 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-1aAlso: RebifIn patients < 26 years after end of radiochemotherapy for 6 months | Drug | 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 |
| MRIAt diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy | Procedure or surgery | 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 |
| PETAt diagnosis and 17 to 22 days after the beginning of cycle 3 of induction therapy, either as PET-CT or PET-MRI | Procedure or surgery | 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 OutcomesFor all patients at baseline, before radiochemotherapy, at day 100, and 2 years after enrolment | Behavioural | 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 |
Primary outcome
Complete remission rate after induction therapy
Time frame: MRI and PET will be done 17-22 days after start of induction therapy cycle 3 (each cycle is 21 days)
Complete response by MRI and PET will be determined as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
3 secondary outcomes
Overall and Event-free Survival
Time frame: 2 years after study enrolment
Number of Treatment-Related Adverse Events
Time frame: 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
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Udo Kontny, MD principal investigator
Uniklinik RWTH Aachen
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Cisplatin and 5-Fluorouracil in people with Nasopharyngeal Carcinoma and Nasopharyngeal Cancer, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 31 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Helena Kerp, PhD (+49 201 74 94 96 14, h.kerp@forschung-paediatrie.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission rate after induction therapy (time frame: MRI and PET will be done 17-22 days after start of induction therapy cycle 3 (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.