Immunotherapy + Chemotherapy for Resectable Head and Neck Cancer

Recruiting at 1 trial location

Overseen By Kartik Sehgal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 19

28 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{1 2 3 5 6}

Research Team

Kartik Sehgal

Principal Investigator

Dana-Farber Cancer Institute

Eligibility 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)

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

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

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Pembrolizumab

Trial Overview 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.

Participant Groups

Group I: Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment Experimental Treatment 4 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. 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

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

Pembrolizumab, either alone or in combination with chemotherapy, shows better efficacy and lower costs compared to cetuximab plus chemotherapy for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

The cost-effectiveness analysis indicates that pembrolizumab strategies yield favorable incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY), making them viable first-line treatment options, especially for patients with PD-L1 combined positive scores (CPS) of ≥1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. She, L., Tian, K., Han, J., et al.[2022]

In a study involving 16 patients with head and neck cancer, the combination of docetaxel and carboplatin during radiotherapy resulted in a high complete response rate of 81%, indicating strong efficacy in treating this type of cancer.

While the treatment was effective, it also led to significant toxicities, including grade 3 mucositis in 69% of patients, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. Karasawa, K., Shinoda, H., Katsui, K., et al.[2018]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

In a phase II study involving 31 patients with advanced squamous cell carcinoma of the head and neck, docetaxel demonstrated significant activity, with a major response rate of 42% and a median response duration of 5 months.

Docetaxel was well tolerated, with manageable side effects such as leukopenia and fatigue, and the use of premedication helped reduce the incidence of severe toxicities, allowing for safe outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. Dreyfuss, AI., Clark, JR., Norris, CM., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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]

4. England pubmed.ncbi.nlm.nih.gov

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]

5. Greece pubmed.ncbi.nlm.nih.gov

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer. [2018]

6. Greece pubmed.ncbi.nlm.nih.gov

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]

7. Greece pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Docetaxel: an active drug for squamous cell carcinoma of the head and neck. [2018]