A Phase 2 Study of Preoperative Pembrolizumab and Chemotherapy Followed by Adjuvant Pembrolizumab in Resectable Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Not specified
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 28
- Locations
- 2
- Primary Endpoint
- Rate of Major Pathological Response (mPR)
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
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)
Detailed Description
This is a Phase II, open-label, non-randomized, single arm, single-center interventional study of neoadjuvant chemoimmunotherapy with pembrolizumab, cisplatin (or carboplatin), and docetaxel followed by surgery followed by adjuvant pembrolizumab therapy in patients with resectable recurrent squamous cell carcinoma of the head and neck (HNSCC). This study will also include individuals with new HNSCC which developed in a field that has received prior radiation therapy. Pembrolizumab works by helping the immune system to fight HNSCC. This research study involves screening for eligibility, study treatment visits including evaluations, radiologic scans, tumor biopsies, and blood tests. The U.S. Food and Drug Administration (FDA) has not approved Pembrolizumab for squamous cell carcinoma of the head and neck (HNSCC) setting before and after surgery, but it has been approved for HNSCC in the advanced incurable setting when surgery is no longer possible or cancer has spread to parts of the body outside the head and neck region. All other drugs used in this study have been approved by the FDA for squamous cell carcinoma of the head and neck (HNSCC) in the advanced incurable setting. Participation in this research study is expected to last for up to 5 years. It is expected that about 28 people will take part in this research study. Merck Sharp \& Dohme LLC is supporting this research study and providing the study drug.
Investigators
Kartik Sehgal, MD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Participants 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
Intervention: Pembrolizumab
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Participants 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
Intervention: CISPLATIN
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Participants 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
Intervention: Carboplatin
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Participants 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
Intervention: Docetaxel
Outcomes
Primary Outcomes
Rate of Major Pathological Response (mPR)
Time Frame: 2 months
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.
Secondary Outcomes
- Grade 3-5 Treatment-related Toxicity Rate(Up to 18 months)
- Median Overall Survival (OS)(Every six months up to 5 years)
- Best Radiological Response Rate(Before Salvage Surgery, upto 10 weeks from study registration)
- Median Disease-Free Survival (DFS)(Every six months up to 5 years)