Clinical trial NCT02296684: Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
Official title: Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cancer of Head and Neck
Head and Neck Cancer
Neoplasms, Head and Neck
Carcinoma, Squamous Cell of Head and Neck
Squamous Cell Carcinoma of the Head and Neck
Squamous Cell Carcinoma, Head and Neck
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-11-20
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this trial is to test the ability of MK-3475 (pembrolizumab) to improve locoregional recurrence and distant metastatic rates in high-risk patients with locally advanced head and neck squamous cell carcinomas (HNSCCs) that are treated with current standard of care surgical approaches.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed stage III or IV HNSCC oral cavity, hypopharynx, oropharynx, larynx (excluding p16 or HPV-positive oropharynx primaries and sinonasal primaries).
* Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam by RECIST 1.1.
* At least 18 years of age.
* ECOG performance status ≤ 1
* Normal bone marrow and organ function as defined below:

  * Absolute neutrophil count ≥ 1,500/mcl
  * Platelets ≥ 100,000/mcl
  * Hemoglobin ≥ 9 g/dL
  * Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN
  * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases)
  * Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 30 mL/min/1.73 m2 for patients with creatinine levels \> 1.5 x IULN
  * INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
  * aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
* Sexually active women of childbearing potential and men must agree to use 2 methods of contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 120 days after last dose of MK-3475. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* Prior treatment for head and neck cancer.
* Patients with HPV-positive or p16-positive oropharyngeal SCCA.
* Patients with sinonasal SCCAs
* Patients with metastatic SCCA neck disease with an unknown primary tumor site
* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
* Received a live vaccine within 30 days prior to the first dose of MK-3475. 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 (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated viruses and are not allowed.
* A history of other malignancy ≤ 3 years previous with the exception of previous head and neck cancer treated only by surgery, basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix.

Note: patients with synchronous head and neck cancer primaries are an exception to this criterion and may qualify for the study.

* 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 the first dose of MK-3475.
* Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of MK-3475.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements.
* 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.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
* Known history of active TB (bacillus tuberculosis).
* Known history of hepatitis B (defined as hepatitis B survace antigen \[HBsAg\] reactive) or known active hepatitis C (defined as HCV RNA \[qualitative\] is detected) infection. Note: know testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
* Known history of HIV (HIV 1/2 antibodies).

Primary outcomes:
measure: Locoregional Recurrence Rates in Cohorts 1 and 2
timeFrame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
measure: Distant Failure Rate in Cohorts 1 and 2
timeFrame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
measure: Rate of Major Pathologic Treatment Effect in Cohort 1
timeFrame: At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
measure: Rate of Major Pathologic Treatment Effect in Cohort 2
timeFrame: At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose)
Secondary outcomes:
measure: Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events
timeFrame: Through 30 days after last dose of MK-3475
measure: Number of Surgical Complications and/or Delays in Cohorts 1 and 2
timeFrame: At the time of surgery (approximately 2-3 weeks after registration)
measure: Locoregional Recurrence Rates in Cohorts 1 and 2
timeFrame: Through completion of follow-up (estimated to be 5 years after treatment)
measure: Rate of Distant Metastases (DM) in Cohorts 1 and 2
timeFrame: Through completion of follow-up (estimated to be 5 years after treatment)
measure: Event-free Survival (EFS) in Cohorts 1 and 2
timeFrame: Through completion of follow-up (estimated to be 5 years after treatment)
measure: Event-free Survival (EFS) Rate Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2
timeFrame: Through completion of follow-up (estimated to be 5 years after treatment)
measure: Overall Survival (OS) Rates Differences by Presence Versus Absence of Recurrent Genomic Alterations in Cohorts 1 and 2
timeFrame: Through completion of follow-up (estimated to be 5 years after treatment)]
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Washington University School of Medicine
name: Douglas R Adkins, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LS, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou L, Jo VY, Stachler MD, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, Adkins DR. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Clin Cancer Res. 2020 Oct 1;26(19):5140-5152. doi: 10.1158/1078-0432.CCR-20-1695. Epub 2020 Jul 14.