MK-3475 (SCH 9000475) as neoadjuvant and adjuvant therapy in Stage III-IVA resectable LA HNSCC (Locoregionally Advanced Head and Neck Squamous Cell Carcinoma)
- Conditions
- Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001139-38-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 704
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Have histologically confirmed new diagnosis of resectable, non-metastatic, squamous cell carcinoma as assessed by the investigator based on baseline imaging and clinical assessment that is either:
a. Stage III oropharyngeal p16 positive that is T4 (N0-N2), M0
OR
b. Stage III or IVA oropharyngeal p16 negative
OR
c. Stage III or IVA larynx/hypopharynx/oral cavity (independent of p16).
2. Be eligible for primary surgery based on investigator decision and per local practice. This decision must be validated by members of a multidisciplinary team, including the surgical oncologist, medical oncologist and radiation oncologist
3. Male/female participants who are at least 18 years of age on the day of signing informed consent
4. A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
5. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) OR
b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.
6. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main study without participating in Future Biomedical Research.
7. Have evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST 1.1 as assessed by the local site investigator/radiology.
8. Have provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for central PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate [FNA] is not
adequate) for stratification prior to randomization. Repeat samples may be required if adequate tissue is not provided. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
9. Have results from (local) testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay (Ventana Medical Systems Inc., Tucson AZ) using standard protocol. Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumor cells. If HPV status was previously tested using this method, no additional testing is required.
10. Have an ECOG performance status of 0 to 1 performed within 10 days of treatment randomization.
11. Have adequate organ function. Specimens must be collected within 10 days prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 352
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 352
Participants are excluded from the study if any of the following criteria apply:
1. Has Stage T4B and/or N3 LA HNSCC and/or distant metastases.
2. Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary HNC.
3. A WOCBP who has a positive urine pregnancy test within 3 days prior to randomization or within 24 hours prior to the start of RT ± cisplatin. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
5. Has received prior radiotherapy treatment or systemic anti-cancer therapy including investigational agents for the HNC under study prior to randomization/allocation.
6. Has received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist® [Influenza Vaccine Live, AstraZeneca]) are live attenuated vaccines and are not allowed.
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization.
8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
10. Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review.
11. Has Grade =2 audiometric hearing loss.
12. Has Grade =2 neuropathy.
13. Has Grade 3-4 bleeding due to the underlying malignancy.
14. If participant has received major surgery, and the participant has not recovered adequately from the toxicity and/or complications from the intervention prior to randomization.
15. Has had previous allogeneic tissue/solid organ transplant.
16. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients, RT or cisplatin or their analogs.
17. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
18. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
19. Has an active infection requiring systemic therapy.
20. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
21. Has a known history of or is positive for Hepatitis B (defined as hepatitis B su
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