Preoperative Pembrolizumab and Chemotherapy in Resectable, Recurrent HNSCC
A Phase 2 Study of Preoperative Pembrolizumab and Chemotherapy Followed by Adjuvant Pembrolizumab in Resectable Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma
1 other identifier
interventional
28
1 country
2
Brief Summary
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2023
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2023
CompletedFirst Posted
Study publicly available on registry
February 13, 2023
CompletedStudy Start
First participant enrolled
May 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 20, 2030
June 22, 2025
June 1, 2025
4.6 years
January 24, 2023
June 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
2 months
Secondary Outcomes (4)
Grade 3-5 Treatment-related Toxicity Rate
Up to 18 months
Median Overall Survival (OS)
Every six months up to 5 years
Median Disease-Free Survival (DFS)
Every six months up to 5 years
Best Radiological Response Rate
Before Salvage Surgery, upto 10 weeks from study registration
Study Arms (1)
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
EXPERIMENTALParticipants will complete study procedures as outlined: Preoperative Phase: * Mandatory biopsy at baseline. * Neoadjuvant treatment (2 cycles): * Cycles 1 - 2 ---Day 1 of 21-day Cycle: Predetermined doses of Pembrolizumab, Cisplatin (or Carboplatin) and Docetaxel. Surgery: -Primary tumor resection and/or lymph node dissection surgery 3-6 weeks from cycle 2 day 1 Adjuvant Phase: -3-8 weeks post-surgery and upto a total of 15 cycles --Cycles 3 - 17 ---Day 1 of 21-day cycle: Predetermined dose of Pembrolizumab Follow up appointments
Interventions
Immunoglobulin G4 monoclonal antibody, via IV infusion
Platinum agent, via IV infusion
Platinum agent, via IV infusion
Antineoplastic agent, via IV infusion.
Eligibility Criteria
You may qualify if:
- 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.
- Participants may have any smoking history (no restrictions)
- Participants may have any Human Papilloma Virus (HPV) status of the tumor. Patients with oropharyngeal cancer are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV PCR or ISH testing
- Age ≥18 years
- ECOG performance status 0 or 1 (Karnofsky ≥70%, see Appendix A)
- Participants must have adequate organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤ institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
- creatinine ≤ institutional ULN OR
- +8 more criteria
You may not qualify if:
- 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).
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
- 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 the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic 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 study drug
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Has a history of allergic reactions to agents used in study
- Has 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
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (2)
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kartik Sehgal, MD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 24, 2023
First Posted
February 13, 2023
Study Start
May 20, 2023
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
May 20, 2030
Last Updated
June 22, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.