Postoperative aRCH With Cisplatin Versus aRCH With Cisplatin and Pembrolizumab in Locally Advanced Head and Neck Squamous Cell Carcinoma

HNSCC Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03480672
• Other study ID #: ADRISK
• Status: Recruiting
• Phase: Phase 2
• Start date: August 6, 2018
• Est. completion date: January 2025

Study information

• Verified date: September 2023
• Source: University of Leipzig
• Contact: Andreas Dietz, Prof. Dr.
• Phone: 0049 34197
• Email: andreas.dietz[@]medizin.uni-leipzig.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• HNSCC
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]
intravenous application, 12 months, in 3-week cycle (q3w) 200 mg

Other:
• adjuvant radiochemotherapy
adjuvant radiochemotherapy with cisplatin

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin; Klinik für Radioonkologie und Strahlentherapie CVK	Berlin
Germany	Charité - Universitätsmedizin, CVK und CCM, Klinik für Hals-Nasen-Ohrenheilkunde	Berlin
Germany	Klinikum Bielefeld, Onkologie/Hämatologie/ Palliativmedizin	Bielefeld
Germany	Universitätsklinikum Bonn; Med. Klinik III / ZIM, Hämatologie/Onkologie	Bonn
Germany	Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und Radiologische Onkologie	Düsseldorf
Germany	Helios Klinikum Erfurt GmbH, Klinik für Hals-Nasen-Ohrenheilkunde	Erfurt
Germany	Universitätsklinikum Essen, Klinik und Poliklinik für Strahlentherapie	Essen
Germany	Kath. Marienkrankenhaus gGmbH, Zentrum für Innere Medizin Hämatologie/Onkologie	Hamburg
Germany	Universitätsklinikum Jena, Klinik für Hals-Nasen-Ohrenheilkunde	Jena
Germany	Department of Head Medicine and Oral Health, University of Leipzig	Leipzig
Germany	UNIVERSITÄTSKLINIKUM Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	Universitätsklinikum Mannheim, Hals-Nasen-Ohren Klinik	Mannheim
Germany	Ernst von Bergmann Klinikum Potsdam, Zentrum für Hämatologie, Onkologie und Strahlenheilkunde, Klinik für Hämatologie und	Potsdam
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie	Regensburg
Germany	Klinikum Stuttgart - Katharinenhospital, Klinik für Radioonkologie und Strahlentherapie	Stuttgart
Germany	Universitätsklinikum Würzburg; Klinik und Poliklinik für Strahlentherapie	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
University of Leipzig

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival (EFS)	time from randomization to the first event (i.e. locoregional or distant recurrence, initiation of a new anti-cancer treatment death from any cause)	24 months
Secondary	Overall survival (OS)	time from randomization to death from any cause	24 months