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-DE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 704
1. Have histologically confirmed new diagnosis of resectable, nonmetastatic,
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 at the time
of providing informed consent.
4. If male, agrees to the following during the intervention period and for
at least the time needed to eliminate each study intervention after the
last dose of study intervention.
The length of time required to continue contraception for each study
intervention is as follows:
- Pembrolizumab: no contraception requirement
- Cisplatin: 180 days
- Radiotherapy: 90 days
•Refrains from donating sperm
PLUS either:
•Abstains from heterosexual intercourse as their preferred and usual
lifestyle and agrees to remain abstinent
OR
•Uses contraception unless confirmed to be azoospermic (vasectomized
or secondary to medical cause, documented from the site personnel's
review of the participant's medical records, medical examination, or
medical history interview) as detailed below:
- Uses a male condom plus partner use of an additional contraceptive
method when having penile-vaginal intercourse with a WOCBP who is
not currently pregnant.
5. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
•Not a WOCBP
OR
•A WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate
of <1% per year), with low user dependency, or be abstinent from
heterosexual intercourse as their preferred and usual lifestyle, during
the intervention period and for at least the time needed to eliminate
each study intervention after the last dose of study intervention and
agrees not to donate eggs (ova, oocytes) to others or freeze/store for
her own use for the purpose of reproduction during this period. The
length of time required to continue contraception for each study
intervention is as follows:
- Pembrolizumab: 120 days
- Cisplatin: 180 days
- Radiotherapy: 180 days
•Has a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 24 hours for urine or within 72
hours for serum before randomization.
•Abstains from breastfeeding during the study intervention period and
for at least 120 days after the last dose of pembrolizumab and 180 days
after the last dose of cisplatin.
•Medical history, menstrual history, and recent sexual activity has been
reviewed by the investigator to decrease the risk for inclusion of a
woman with an early undetected pregnancy.
6. The participant (or legally acceptable representative) provides
documented 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 o
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 pregnancy test within 24 hours (urine)
or within 72 hours (serum) before 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-PDL2
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 anticancer
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 surface antigen [HBsAg] reactive) or known active Hepati
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