Immunotherapy + Chemotherapy for Resectable Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Dana-Farber Cancer Institute
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Metastatic disease, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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)
Do I need to stop my current medications to join the trial?
The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have recently received certain vaccines, you may need to discuss this with the trial team.
What data supports the effectiveness of the drug combination used in the clinical trial for head and neck cancer?
Research shows that the combination of docetaxel and cisplatin is effective in treating advanced head and neck cancer, and pembrolizumab has been approved for use in similar conditions, improving survival rates when combined with chemotherapy.
12345Is the combination of immunotherapy and chemotherapy safe for head and neck cancer?
The combination of pembrolizumab (an immunotherapy drug) with carboplatin and paclitaxel (chemotherapy drugs) was generally well tolerated in a small study of patients with head and neck cancer, although all patients experienced mild side effects, and 30% had more serious side effects like anemia (low red blood cell count) and high blood pressure.
16789How is the drug combination of immunotherapy and chemotherapy unique for treating resectable head and neck cancer?
This treatment combines immunotherapy (pembrolizumab) with chemotherapy drugs (carboplatin, cisplatin, and docetaxel), which is unique because it leverages the immune system to target cancer cells while also using chemotherapy to directly kill them. This combination aims to improve outcomes by enhancing the body's immune response against cancer, which is different from traditional chemotherapy alone.
12356Eligibility Criteria
Adults with recurrent head and neck squamous cell carcinoma (HNSCC) eligible for surgery, not pregnant or breastfeeding, willing to use contraception. Must have good organ function, no recent immunotherapy or live vaccines, no other active cancers or severe autoimmune diseases. No prior treatment within 6 months and must be able to provide tissue samples.Inclusion Criteria
I am a male and agree to follow the specified contraception guidelines for 180 days after my last treatment dose.
Because pembrolizumab and chemotherapy can be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Participants may have any smoking history (no restrictions)
+11 more
Exclusion Criteria
I have received a transplant from another person.
I received treatment for head and neck cancer less than 6 months ago.
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
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Preoperative Treatment
Participants receive neoadjuvant treatment with Pembrolizumab, Cisplatin (or Carboplatin), and Docetaxel for 2 cycles
6 weeks
2 visits (in-person)
Salvage Surgery
Primary tumor resection and/or lymph node dissection surgery
3-6 weeks after cycle 2 day 1
1 visit (in-person)
Adjuvant Treatment
Participants receive adjuvant Pembrolizumab therapy for up to 15 cycles
45 weeks
15 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Every six months up to 5 years
Regular follow-up visits
Participant Groups
The trial is testing the combination of pembrolizumab (immunotherapy) with chemotherapy drugs cisplatin, carboplatin, and docetaxel before and after surgery in patients with HNSCC. Pembrolizumab continues for about a year post-surgery to assess effectiveness and safety.
1Treatment groups
Experimental Treatment
Group I: Pre-Operative Treatment + Salvage Surgery + Adjuvant TreatmentExperimental Treatment4 Interventions
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.
Salvage 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
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
Dana-Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
Dana-Farber Cancer InstituteLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial.
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.
Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. [2020]Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.
Pembrolizumab with or without chemotherapy versus cetuximab plus chemotherapy to treat recurrent or metastatic head and neck squamous cell carcinoma: An updated KEYNOTE-048 based cost-effectiveness analysis. [2022]Recently, updated data from KEYNOTE-048 revealed that pembrolizumab with or without chemotherapy could improve progression-free survival (PFS)2 compared with cetuximab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. [2018]This study was designed to evaluate the concomitant use of docetaxel and carboplatin for radiosensitization in head and neck cancer.
Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. [2023]Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.
Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities.
The role of docetaxel in the management of squamous cell cancer of the head and neck. [2018]The activity of docetaxel (Taxotere) as a single agent (overall response rates, 24%-45%) in the treatment of patients with recurrent squamous cell cancer of the head and neck has resulted in the investigation of docetaxel-based doublet and triplet combinations in both the recurrent and neoadjuvant settings. When combined with cisplatin, with or without fluorouracil (5-FU), in the treatment of recurrent disease, response rates of 33% to 44% have been observed for docetaxel, with median survival ranging from 9.6 to 11 months. In the neoadjuvant setting, response rates have been typically greater than 90%, with promising disease-free and overall survival results. Randomized trials are now under way to assess the value of docetaxel-based therapy relative to that of the standard cisplatin/5-FU combination in both the neoadjuvant and recurrent settings. Preclinical data indicate that docetaxel is a potent radiosensitizer and its initial evaluation with concurrent radiation in patients with locally advanced unresectable squamous cell cancer of the head and neck suggests feasibility. Phase II evaluation of this approach is in progress.
Docetaxel: an active drug for squamous cell carcinoma of the head and neck. [2018]We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhône-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy.