E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced primary resectable stage III, IVA/B head and neck squamous cell carcinoma (HNSCC) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced head and neck squamous cell carcinoma (HNSCC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To show that addition of Pembrolizumab (P) to postoperative adjuvant radiochemotherapy (aRCH) with Cisplatin (C) improves event free survival (EFS) compared with aRCH alone in locally advanced intermediate and high risk head and neck squamous cell carcinoma (HNSCC) |
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E.2.2 | Secondary objectives of the trial |
To show that addition of Pembrolizumab (P) to postoperative adjuvant radiochemotherapy (aRCH) with Cisplatin (C) improves overall survival (OS) compared with aRCH alone in locally advanced intermediate and high risk head and neck squamous cell carcinoma (HNSCC). To assess toxicity and show that addition of Pembrolizumab (P) to postoperative adjuvant radiochemotherapy (aRCH) with Cisplatin (C) is safe in terms of toxicity.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Macroscopically complete resection of newly diagnosed 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 performance status of 0 to 1 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 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 as outlined in Section 5.5.2, 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 as outlined in Section 5.5.2, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
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E.4 | Principal 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. a. Note: Subjects with ≤ Grade 2 (NCI CTCAE Grade) neuropathy are an exception to this criterion and may qualify for the study. b. 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. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. 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 site
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Event Free Survival (EFS) defined as time from randomization to the first event, i.e.: • locoregional or distant recurrence (relapse), • occurrence of further malignoma (independent from localization and type), • death from any cause, and • initiation of a new anti-cancer treatment without a previous EP-event (primarily in case of safety concerns/toxicities observed which must be addressed in patient’s treatment).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from randomization to the first event |
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E.5.2 | Secondary end point(s) |
Overall survival (OS) is defined as time from randomization to death from any cause. OS is the most relevant outcome; Adverse events/Toxicity according to NCI-CTC AE criteria |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
from randomization to death |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
in both treatment arms adjuvant radiochemotherapy according national guidelines (=standard therapy) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |