This research study is evaluating effectiveness and safety of a combination of immunotherapy drug, pembrolizumab, with chemotherapy, as a possible treatment before and after surgery for squamous cell carcinoma of the head and neck (HNSCC). The combination of pembrolizumab and chemotherapy will be given prior to your surgery, while immunotherapy pembrolizumab will be continued for approximately 1 year after surgery.
The names of the study drugs involved in this research study are:
* pembrolizumab (a type of immunotherapy) * docetaxel (a type of chemotherapy) * cisplatin (a type of chemotherapy) * carboplatin (a type of chemotherapy)
Participants must have histologically or cytologically confirmed locoregionally recurrent squamous cell carcinoma of the head and neck, or second primary HNSCC in a previously irradiated field, defined as >50% of the presurgical tumor volume having prior radiation dose of >45 Gy as determined by the treating radiation oncologist (including primary sites, such as oral cavity, oropharynx, larynx or hypopharynx carcinoma).
Participants must be a candidate for curative intent surgery.
Participants must have documented time of ≥ 6 months from completion of prior curative intent treatment for HNSCC (surgery and/or radiation therapy with/without platinum chemotherapy or cetuximab targeted therapy) to diagnosis of local or locoregional recurrence or a second primary in a previously irradiated field.
Participants must be willing to undergo a mandatory pre-treatment biopsy and willing to provide blood and tissue from the pre-treatment biopsy and at the time of surgery. Exceptions may be made after discussion with sponsor if it is not medically feasible to obtain a pre-treatment biopsy or is in the best interest of the patient. Archival tissue may be collected in this situation. Participants will be offered the opportunity to volunteer for optional biopsies at the time of recurrence of disease.
Sinonasal, nasopharyngeal or cutaneous primary site of squamous cell carcinoma of the head and neck
Has known distant metastatic disease. Those with known brain metastases should be excluded from this clinical trial, because of the poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, baseline brain imaging is not required prior to enrollment in the study if patients are asymptomatic
Has had chemotherapy or radiotherapy for HNSCC in curative intent setting within 6 months prior to entering the study.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
Single group
Pembrolizumab
DrugImmunoglobulin G4 monoclonal antibody, via IV infusion
CISPLATIN
DrugPlatinum agent, via IV infusion
Carboplatin
DrugPlatinum agent, via IV infusion
Docetaxel
DrugAntineoplastic agent, via IV infusion.
Rate of Major Pathological Response (mPR)
Major pathologic response (mPR) is defined as having ≤ 10% invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes as assessed by pathologists. Rate is the proportion of treated participants who experienced mPR.
Grade 3-5 Treatment-related Toxicity Rate
Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation. All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted.
Median Overall Survival (OS)
OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Median Disease-Free Survival (DFS)
Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from surgery to the first recurrence or death from any cause, whichever occurs first. Participants alive without disease recurrence are censored at date of last disease evaluation.
Best Radiological Response Rate
Best radiological response are based on the RECIST 1.1 criteria, defined protocol section 11.2.4.
Click on the lead sponsor to view all of their trials.
Dana-Farber Cancer Institute
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
