Pembrolizumab or placebo in combination with chemoradiation (CRT) in subjects with locally advanced HNSCC

Phase 1

Conditions: ocally advanced head and neck squamous cell carcinoma (LA HNSCC)
MedDRA version: 21.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-003934-25-IT

Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 780

Inclusion Criteria

1. Have a pathologically proven new diagnosis of squamous cell carcinoma of:
a. Oropharyngeal p16 positive
i. T4 (N0-N3), M0 ; or
ii. N3 (T1-T4), M0
OR
b. Oropharyngeal p16 negative
i. any T3-4 (N0-N3), M0 ; or
ii. any N2a-3 (T1-T4), M0
OR
c. Larynx/hypopharynx/oral cavity (independent of p16)
i. any T3-4 (N0-N3), M0 ; or
ii. any N2a-3 (T1-T4), M0
2. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
3. Have results from (local) testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point. If HPV status was previously tested using this method, no additional testing is required.
4. Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate [FNA] is not adequate).
5. Be >=18 years of age on day of signing informed consent.
6. Have evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan or MRI, based on RECIST version 1.1.
7. Be eligible for definitive CRT and not considered for primary surgery based on investigator decision.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 performed within 10 days of treatment initiation.
9. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
10. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the protocol, for the course of the study through 180 days after the last dose of study medication.
11. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 180 days after the last dose of study therapy.
12. Demonstrate adequate organ function as defined in the protocol. All screening labs should be performed within 10 days of treatment initiation and assessed prior to randomizing the subject.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

1. Has current participation or treatment with an investigational agent or use of an investigational device within 4 weeks of the first dose of trial treatment.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137 or other immune checkpoint inhibitors) or has previously participated in Merck MK-3475 clinical trials.
3. Has received a live vaccine within 30 days prior to the first dose of study treatment.
4. Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary HNC.
5. Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for the head and neck cancer under study.
6. Has Grade >=2 audiometric hearing loss (25 decibels in 2 consecutive wave ranges).
7. Has Grade >=2 neuropathy.
8. Has Grade 3-4 bleeding due to the underlying malignancy.
9. If subject has received major surgery, the subject have not recovered adequately form the toxicity and/or complications form the intervention prior to starting trial treatment.
10. Has known active Hepatitis B (e.g., HBsAg reactive) or C (e.g., HCV RNA [qualitative] is detected).
11. Has known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
12. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Corticosteroid use as pre-medication for allergic reactions (e.g. IV contrast), or as a prophylactic management of adverse events related to the chemotherapies specified in the protocol is allowed. A short course of steroids may be used as concomitant medication for either treatment an advers event or medical condition with Sponsor approval.
13. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
14. Has an active autoimmune disease that has required systemic treatment in the past 2 years (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.
15. Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization. A T1-2 prostatic cancer Gleason score =6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix is eligible. Other exceptions may be considered with Sponsor consultation.
16. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
17. Has had previous allogeneic tissue/solid organ transplant.
18. Has active infection requiring systemic therapy.
19. Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to pembrolizumab, cisplatin or radiotherapy or their analogs.
For criteria #20, #21, #22 and #23 refer to protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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