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Head and Neck CancerPhase 3IMSTAR-HNNCT03700905

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

A Phase 3 study testing Surgical resection of primary tumor, Adjuvant radio(-chemo)therapy and Neoadjuvant Nivolumab in people with Head and Neck Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 7 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
Surgical resection of primary tumor, Adjuvant radio(-chemo)therapy and Neoadjuvant Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
276 participants
Where
7 sitesGermany
Study dates
21 Aug 2018to May 2024
Phase
Phase 3
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Klinikum Bielefeld

    Bielefeld, North Rhine-Westphalia, 330604

  • HELIOS Klinikum Erfurt GmbH

    Erfurt, Thuringia, 99089

  • Universitätsklinikum Gießen

    Giessen, Hesse, 35392

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Katholisches Marienkrankenhaus Hamburg

    Hamburg, 22087

  • Technische Universität München, Klinikum rechts der Isar

    München, Bavaria, 81675

  • Universitätsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89075

Other trials in Germany

About this study

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

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

Read the 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.

Being tested
Surgical resection of primary tumor, Adjuvant radio(-chemo)therapy, Neoadjuvant Nivolumab, Adjuvant Nivolumab, Adjuvant Nivolumab and Ipilimumab
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Surgical resection of primary tumorProcedure or surgery

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

  • Adjuvant radio(-chemo)therapyRadiation

    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)

  • Neoadjuvant NivolumabDrug

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

  • Adjuvant NivolumabDrug

    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

  • Adjuvant Nivolumab and IpilimumabDrug

    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 groups in NCT03700905
Study groupRoleWhat they receive
Neoadjuvant/adjuvant Nivolumab and IpilimumabExperimental* 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
Receives: Procedure: Surgical resection of primary tumor; Radiation: Adjuvant radio(-chemo)therapy; Drug: Neoadjuvant Nivolumab; Drug: Adjuvant Nivolumab; Drug: Adjuvant Nivolumab and Ipilimumab
Surgical resection + adjuvant radio(-chemo)therapyActive comparator* 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
Receives: Procedure: Surgical resection of primary tumor; Radiation: Adjuvant radio(-chemo)therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival

    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

    Measured: approximately 71 months

Secondary outcomes (8)

  1. Local regional control (LRC)

    Disease assessment (CT/ MRI) and Panendoscopy and FFPE in case of suspicion or recurrence

    Measured: Time from randomization to date of first observed histologically proven or death, up to 36 month

  2. Distant metastasis free survival (DMFS)

    Disease assessment (CT/ MRI)

    Measured: Time from randomization to date of first observed histologically proven or death, up to 36 month

  3. Overall survival (OS)

    Follow Up- Visits after end of treatment every 3 months until month 36 after randomization, afterwards every 6 months

    Measured: until end of study (36 months after end of therapy of the last patient), approximately 71 months

  4. Acute toxicity and late morbidity

    Adverse Events Assessment

    Measured: AEs/SAEs should be collected continuously until 12 months after randomization

  5. Quality of life (QoL): QLQ-C30

    Questionaire EORTC QLQ-C30

    Measured: through study completion, an average of 3 years

  6. Quality of life (QoL): Questionnaire H&N43

    Questionnaire H\&N43

    Measured: through study completion, an average of 3 years

  7. Comparison of nivolumab alone group vs control and nivolumab & ipilimumab group vs control in terms of DFS

    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

    Measured: assessed up to 36 month

  8. Survival depending on PD-L1 Status

    Assessment of PD-L1 Status

    Measured: after surgery, up to 4 weeks after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start21 Aug 2018
  3. Primary completionMay 2024 (estimated)
  4. Study completionMay 2024 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Enrolment
276 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03700905
Sponsor's protocol ID
CA209-934
Acronym
IMSTAR-HN
Status last verified
May 2023
First submitted
3 Aug 2018
Last updated
23 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 19156911

  • 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.

    PubMed 21911310

  • Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren 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.

    PubMed 26028407

  • 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, Lebbe 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.

    PubMed 25399552

  • 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.

    PubMed 25891173

  • 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.

    PubMed 27247226

  • 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. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.

    PubMed 27718784

  • 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.

    PubMed 28939078

  • 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.

    PubMed 32902312

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Surgical resection of primary tumor, Adjuvant radio(-chemo)therapy and Neoadjuvant Nivolumab in people with Head and Neck Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 7 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 22 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (time frame: approximately 71 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03700905, which also lists 9 linked publications.

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 23 May 2023; AzTrials last refreshed its copy on 7 Nov 2026.

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