4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy (IMSTAR-HN)

Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy (IMSTAR-HN)

Study Description
Brief Summary:
Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Procedure: Surgical resection of primary tumor Radiation: Adjuvant radio(-chemo)therapy Drug: Neoadjuvant Nivolumab Drug: Adjuvant Nivolumab Drug: Adjuvant Nivolumab and Ipilimumab Phase 3

Detailed Description:
Surgically treated locally advanced head and neck squamous cell carcinoma often requires postoperative chemoradiation with high risk of acute and late toxicity. DFS after 2 years is approximately 70%. Combining anti-PD-1 and anti-CTLA4 as a maintenance therapy may improve DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor antigens.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Arm Ia and Arm Ib are summarized in one Arm, due to central ethics committee, as they both include neoadjuvant and adjuvant treatment compared to Arm II
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Randomized Controlled Phase III Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy
Actual Study Start Date : August 21, 2018
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Neoadjuvant/adjuvant Nivolumab and Ipilimumab
  • Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery
  • Surgical resection of primary tumor including neck dissection according to standard of care
  • 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only), start within 6 weeks post-surgery

Arm Ia:

• Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

Arm Ib:

• Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

 Procedure: Surgical resection of primary tumor
Surgical resection of primary tumor including neck dissection according to standard of care

Radiation: Adjuvant radio(-chemo)therapy
Risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only)

Drug: Neoadjuvant Nivolumab
Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery

Drug: Adjuvant Nivolumab
Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

Drug: Adjuvant Nivolumab and Ipilimumab
Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months
Active Comparator: Surgical resection + adjuvant radio(-chemo)therapy
  • Surgical resection of primary tumor including neck dissection according to standard of care
  • 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (40mg/m2) in high risk patients), start within 6 weeks post-surgery
  • Standard follow-up
 Procedure: Surgical resection of primary tumor
Surgical resection of primary tumor including neck dissection according to standard of care

Radiation: Adjuvant radio(-chemo)therapy
Risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only)
Outcome Measures
Primary Outcome Measures :
  1. Disease Free Survival [ Time Frame: approximately 71 months ]
    disease free survival (DFS) at 3 years of nivolumab alone or in combination with ipilimumab as adjuvant immunotherapy after adjuvant radio(chemo)therapy in locally advanced resected HNSCC


Secondary Outcome Measures :
  1. Local regional control (LRC) [ Time Frame: Time from randomization to date of first observed histologically proven or death, up to 36 month ]
    Disease assessment (CT/ MRI) and Panendoscopy and FFPE in case of suspicion or recurrence

  2. Distant metastasis free survival (DMFS) [ Time Frame: Time from randomization to date of first observed histologically proven or death, up to 36 month ]
    Disease assessment (CT/ MRI)

  3. Overall survival (OS) [ Time Frame: until end of study (36 months after end of therapy of the last patient), approximately 71 months ]
    Follow Up- Visits after end of treatment every 3 months until month 36 after randomization, afterwards every 6 months

  4. Acute toxicity and late morbidity [ Time Frame: AEs/SAEs should be collected continuously until 12 months after randomization ]
    Adverse Events Assessment

  5. Quality of life (QoL): QLQ-C30 [ Time Frame: through study completion, an average of 3 years ]
    Questionaire EORTC QLQ-C30

  6. Quality of life (QoL): Questionnaire H&N43 [ Time Frame: through study completion, an average of 3 years ]
    Questionnaire H&N43

  7. Comparison of nivolumab alone group vs control and nivolumab & ipilimumab group vs control in terms of DFS [ Time Frame: assessed up to 36 month ]
    We compare disease free survival, defined as time from randomization to date of first observed either histologically proven recurrence (local, locoregional or distant), or death from any cause whatever occurs first, of arm Ia to arm II and of arm Ib to arm II

  8. Survival depending on PD-L1 Status [ Time Frame: after surgery, up to 4 weeks after surgery ]
    Assessment of PD-L1 Status


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven SCC of the oropharynx, oral cavity, hypopharynx, and larynx (not older than 3 months before randomization)
  • clinical stage III-IVB (T1, N2-3; T2, N2-3; T3, N0-3; T4a, N0-3)
  • Oropharyngeal cancer HPV-negative (p16 immunohistochemistry negative)
  • Primary tumor and neck metastasis must be resectable
  • Written and signed informed consent
  • Performance Status of 0 or 1 using ECOG
  • Male and female with age ≥ 18
  • Curative treatment intent (cM0)

  • Screening laboratory values must meet the following criteria and should be obtained within 4 weeks prior to randomization

    • WBC ≥ 2000/μL
    • Neutrophils ≥ 1500/μL
    • Platelets ≥ 100 x103/μL
    • Hemoglobin > 9.0 g/dL
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
    • Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
    • Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
    • AST/ALT ≤ 3 x ULN
    • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Women of childbearing potential (WOCBP)1 must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
  • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.

Exclusion Criteria:

  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  • Patients should be excluded if they have had 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 costimulation or immune checkpoint pathways
  • Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
  • Unknown primary (CUP), nasopharyngeal or salivary gland cancer
  • Distant metastatic disease or adenopathy below the clavicles
  • Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C. If clinically suspected, further diagnostic is indicated according to the judgement of the investigator.
  • Pregnancy or lactation
  • Women of child-bearing potential with unclear contraception
  • Previous treatment for the study cancer with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
  • Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Allergies and Adverse Drug Reaction: History of severe hypersensitivity reaction to any monoclonal antibody
  • History of allergy to study drug components
  • Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol
  • Patients institutionalized by official means or court order
  • Deficient dental preservation status or not accomplished wound healing
Contacts and Locations

Locations
Layout table for location information
Germany
Universitätsklinikum Ulm
Ulm, Baden-Württemberg, Germany, 89075
Technische Universität München, Klinikum rechts der Isar
München, Bayern, Germany, 81675
Universitätsklinikum Gießen
Gießen, Hessen, Germany, 35392
Klinikum Bielefeld
Bielefeld, Nordrhein-Westfalen, Germany, 330604
HELIOS Klinikum Erfurt GmbH
Erfurt, Thüringen, Germany, 99089
Universitätsklinikum Hamburg Eppendorf
Hamburg, Germany, 20246
Katholisches Marienkrankenhaus Hamburg
Hamburg, Germany, 22087
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
University Hospital, Essen
Westpfalz-Clinical Center GmbH
Charite University, Berlin, Germany
Investigators
Layout table for investigator information
Principal Investigator: PD Dr. med. Chia-Jung Busch Universitätsklinikum Hamburg-Eppendorf
Tracking Information
First Submitted Date  ICMJE August 3, 2018
First Posted Date  ICMJE October 9, 2018
Last Update Posted Date December 11, 2020
Actual Study Start Date  ICMJE August 21, 2018
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2018) 		Disease Free Survival [ Time Frame: approximately 71 months ]
disease free survival (DFS) at 3 years of nivolumab alone or in combination with ipilimumab as adjuvant immunotherapy after adjuvant radio(chemo)therapy in locally advanced resected HNSCC
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2018)
  • Local regional control (LRC) [ Time Frame: Time from randomization to date of first observed histologically proven or death, up to 36 month ]
    Disease assessment (CT/ MRI) and Panendoscopy and FFPE in case of suspicion or recurrence
  • Distant metastasis free survival (DMFS) [ Time Frame: Time from randomization to date of first observed histologically proven or death, up to 36 month ]
    Disease assessment (CT/ MRI)
  • Overall survival (OS) [ Time Frame: until end of study (36 months after end of therapy of the last patient), approximately 71 months ]
    Follow Up- Visits after end of treatment every 3 months until month 36 after randomization, afterwards every 6 months
  • Acute toxicity and late morbidity [ Time Frame: AEs/SAEs should be collected continuously until 12 months after randomization ]
    Adverse Events Assessment
  • Quality of life (QoL): QLQ-C30 [ Time Frame: through study completion, an average of 3 years ]
    Questionaire EORTC QLQ-C30
  • Quality of life (QoL): Questionnaire H&N43 [ Time Frame: through study completion, an average of 3 years ]
    Questionnaire H&N43
  • Comparison of nivolumab alone group vs control and nivolumab & ipilimumab group vs control in terms of DFS [ Time Frame: assessed up to 36 month ]
    We compare disease free survival, defined as time from randomization to date of first observed either histologically proven recurrence (local, locoregional or distant), or death from any cause whatever occurs first, of arm Ia to arm II and of arm Ib to arm II
  • Survival depending on PD-L1 Status [ Time Frame: after surgery, up to 4 weeks after surgery ]
    Assessment of PD-L1 Status
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy
Official Title  ICMJE Multicenter Randomized Controlled Phase III Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy
Brief Summary Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy
Detailed Description Surgically treated locally advanced head and neck squamous cell carcinoma often requires postoperative chemoradiation with high risk of acute and late toxicity. DFS after 2 years is approximately 70%. Combining anti-PD-1 and anti-CTLA4 as a maintenance therapy may improve DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor antigens.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Arm Ia and Arm Ib are summarized in one Arm, due to central ethics committee, as they both include neoadjuvant and adjuvant treatment compared to Arm II
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Cancer
Intervention  ICMJE
  • Procedure: Surgical resection of primary tumor
    Surgical resection of primary tumor including neck dissection according to standard of care
  • Radiation: Adjuvant radio(-chemo)therapy
    Risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only)
  • Drug: Neoadjuvant Nivolumab
    Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery
  • Drug: Adjuvant Nivolumab
    Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months
  • Drug: Adjuvant Nivolumab and Ipilimumab
    Administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months
Study Arms  ICMJE
  • Experimental: Neoadjuvant/adjuvant Nivolumab and Ipilimumab
    • Neoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery
    • Surgical resection of primary tumor including neck dissection according to standard of care
    • 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only), start within 6 weeks post-surgery

    Arm Ia:

    • Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

    Arm Ib:

    • Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months

    Interventions:
    • Procedure: Surgical resection of primary tumor
    • Radiation: Adjuvant radio(-chemo)therapy
    • Drug: Neoadjuvant Nivolumab
    • Drug: Adjuvant Nivolumab
    • Drug: Adjuvant Nivolumab and Ipilimumab
  • Active Comparator: Surgical resection + adjuvant radio(-chemo)therapy
    • Surgical resection of primary tumor including neck dissection according to standard of care
    • 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (40mg/m2) in high risk patients), start within 6 weeks post-surgery
    • Standard follow-up
    Interventions:
    • Procedure: Surgical resection of primary tumor
    • Radiation: Adjuvant radio(-chemo)therapy
Publications *
  • Gold KA, Lee HY, Kim ES. Targeted therapies in squamous cell carcinoma of the head and neck. Cancer. 2009 Mar 1;115(5):922-35. doi: 10.1002/cncr.24123. Review.
  • Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol. 2011 Dec;47(12):1148-53. doi: 10.1016/j.oraloncology.2011.08.007. Epub 2011 Sep 10.
  • Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.
  • Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-30. doi: 10.1056/NEJMoa1412082. Epub 2014 Nov 16.
  • Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A; KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015 Jun 25;372(26):2521-32. doi: 10.1056/NEJMoa1503093. Epub 2015 Apr 19.
  • Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016 Jul;17(7):956-965. doi: 10.1016/S1470-2045(16)30066-3. Epub 2016 May 27.
  • Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. Epub 2016 Oct 8.
  • Hanna GJ, Adkins DR, Zolkind P, Uppaluri R. Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma. Oral Oncol. 2017 Oct;73:65-69. doi: 10.1016/j.oraloncology.2017.08.008. Epub 2017 Aug 17. Review.
  • Zech HB, Moeckelmann N, Boettcher A, Muenscher A, Binder M, Vettorazzi E, Bokemeyer C, Schafhausen P, Betz CS, Busch CJ. Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma. Future Oncol. 2020 Dec;16(36):3035-3043. doi: 10.2217/fon-2020-0595. Epub 2020 Sep 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2018) 		276
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically proven SCC of the oropharynx, oral cavity, hypopharynx, and larynx (not older than 3 months before randomization)
  • clinical stage III-IVB (T1, N2-3; T2, N2-3; T3, N0-3; T4a, N0-3)
  • Oropharyngeal cancer HPV-negative (p16 immunohistochemistry negative)
  • Primary tumor and neck metastasis must be resectable
  • Written and signed informed consent
  • Performance Status of 0 or 1 using ECOG
  • Male and female with age ≥ 18
  • Curative treatment intent (cM0)

  • Screening laboratory values must meet the following criteria and should be obtained within 4 weeks prior to randomization

    • WBC ≥ 2000/μL
    • Neutrophils ≥ 1500/μL
    • Platelets ≥ 100 x103/μL
    • Hemoglobin > 9.0 g/dL
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
    • Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
    • Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
    • AST/ALT ≤ 3 x ULN
    • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Women of childbearing potential (WOCBP)1 must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
  • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.

Exclusion Criteria:

  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  • Patients should be excluded if they have had 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 costimulation or immune checkpoint pathways
  • Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
  • Unknown primary (CUP), nasopharyngeal or salivary gland cancer
  • Distant metastatic disease or adenopathy below the clavicles
  • Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C. If clinically suspected, further diagnostic is indicated according to the judgement of the investigator.
  • Pregnancy or lactation
  • Women of child-bearing potential with unclear contraception
  • Previous treatment for the study cancer with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
  • Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Allergies and Adverse Drug Reaction: History of severe hypersensitivity reaction to any monoclonal antibody
  • History of allergy to study drug components
  • Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol
  • Patients institutionalized by official means or court order
  • Deficient dental preservation status or not accomplished wound healing
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03700905
Other Study ID Numbers  ICMJE CA209-934
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Universitätsklinikum Hamburg-Eppendorf
Study Sponsor  ICMJE Universitätsklinikum Hamburg-Eppendorf
Collaborators  ICMJE
  • University Hospital, Essen
  • Westpfalz-Clinical Center GmbH
  • Charite University, Berlin, Germany
Investigators  ICMJE
Principal Investigator: PD Dr. med. Chia-Jung Busch Universitätsklinikum Hamburg-Eppendorf
PRS Account Universitätsklinikum Hamburg-Eppendorf
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

治疗案例

前沿医讯