Clinical trial NCT03480672: Postoperative aRCH With Cisplatin Versus aRCH With Cisplatin and Pembrolizumab in Locally Advanced Head and Neck Squamous Cell Carcinoma
Official title: Postoperative Adjuvant Radiochemotherapy (aRCH) With Cisplatin (C) Versus aRCH With C and Pembrolizumab (P) in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC); Multicenter Randomized Phase II Study Within the German Interdisciplinary Study Group of German Cancer Society (IAG KHT); Pembro-Adjuvant-highRisk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HNSCC
Lead sponsor: University of Leipzig
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial evaluates the addition of pembrolizumab to standard postoperative adjuvant radiochemotherapy in the treatment of patients with locally advanced intermediate and high risk head and neck squamous cell carcinoma (HNSCC).


Eligibility criteria: Inclusion Criteria:

1. Macroscopically complete resection of newly diagnosed (not recurrent, not secondary primary) advanced squamous-cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx
2. Advanced stage III, IVA/B HNSCC according to the TNM classification version 7th edition (Note! The 8th edition will not be used, please adhere to the national cancer institute guidelines)
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; performance status allows adjuvant chemo radiation with cisplatin.
4. Had either intermediate or high-risk characteristics, i.e. any or all of the following:

   * histologic evidence of invasion of two or more regional lymph nodes
   * extracapsular extension of nodal disease,
   * microscopically involved mucosal margins of resection (R1) or margins of resection \< 5mm (R0)
5. Had pathological histologic assessment of p16 (only oropharyngeal carcinoma)
6. Be \> 18 years of age
7. Written informed consent
8. Demonstrate adequate organ function
9. Female subject of childbearing potential should have a negative pregnancy test within 3 days prior to receiving the first dose of study medication.
10. Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication.
11. Reproductive male subjects must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria:

1. Concurrent participation in any other interventional clinical trial or participation in any other interventional trial within one month before enrolment into this trial.
2. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before enrolment into this trial.
3. Known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to Pembrolizumab or comparable medicinal products or any of its excipients.
5. Prior anti-cancer monoclonal antibody (mAb) therapy within one month before enrolment into this trial or who has not recovered (i.e., ≤ Grade 1 (NCI CTCAE Grade) at baseline) from adverse events due to agents administered more than one month earlier.
6. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within one month before enrolment into this trial or who has not recovered (i.e., ≤ grade 1 (NCI CTCAE Grade) at baseline) from adverse events due to a previously administered agent.

   1. Note: Subjects with ≤ Grade 2 (NCI CTCAE Grade) neuropathy are an exception to this criterion and may qualify for the study.
   2. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
7. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Active autoimmune disease that has required systemic treatment in the past 2 years prior to enrolment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9. Evidence of interstitial lung disease or history of (non-infectious) pneumonitis that required steroids within the last 6 months before enrolment into this trial, or current pneumonitis.
10. Active infection requiring systemic therapy.
11. Suspected lack of compliance
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the baseline visit through 120 days after the last dose of trial treatment.
13. HIV, HBV or HCV infection
14. Application of a live vaccine within one month of enrolment.
15. Hypersensitivity to cisplatin or any of its excipients
16. Any potential relationship to the investigator/his deputy or to medical staff of the study team, to the coordinating investigator or is an employee of the study sit

Primary outcomes:
measure: Event Free Survival (EFS)
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin; Klinik für Radioonkologie und Strahlentherapie CVK
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin, CVK und CCM, Klinik für Hals-Nasen-Ohrenheilkunde
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld, Onkologie/Hämatologie/ Palliativmedizin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn; Med. Klinik III / ZIM, Hämatologie/Onkologie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und Radiologische Onkologie
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt GmbH, Klinik für Hals-Nasen-Ohrenheilkunde
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik und Poliklinik für Strahlentherapie
city: Hamburg
country: Germany
facility: Kath. Marienkrankenhaus gGmbH, Zentrum für Innere Medizin Hämatologie/Onkologie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Hals-Nasen-Ohrenheilkunde
city: Leipzig
country: Germany
facility: Department of Head Medicine and Oral Health, University of Leipzig
city: Lübeck
country: Germany
facility: UNIVERSITÄTSKLINIKUM Schleswig-Holstein, Campus Lübeck
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, Hals-Nasen-Ohren Klinik
city: Potsdam
country: Germany
facility: Ernst von Bergmann Klinikum Potsdam, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde, Klinik für Hämatologie und
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart - Katharinenhospital, Klinik für Radioonkologie und Strahlentherapie
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg; Klinik und Poliklinik für Strahlentherapie
Study officials:
affiliation: University Leipzig
name: Andreas Dietz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: