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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining an immunotherapy drug, pembrolizumab, with chemotherapy to treat squamous cell carcinoma, a type of head and neck cancer. The plan involves using both treatments before surgery to shrink the tumor and continuing pembrolizumab alone after surgery to prevent recurrence. Individuals whose head and neck cancer has returned in the same area after radiation therapy and who are eligible for surgery might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, a type of immunotherapy, is FDA-approved for certain head and neck cancers. In studies involving 192 patients with head and neck cancer, most tolerated it well, and it was found to be safe.

For the chemotherapy drugs in this trial, cisplatin plays a crucial role and is FDA-approved for head and neck cancer. Many studies have demonstrated its effectiveness and safety. Carboplatin is another chemotherapy drug, and research indicates that patients with head and neck cancer usually tolerate it well.

Docetaxel, also used in this trial, is a chemotherapy drug approved for head and neck cancer. However, it can cause serious side effects, such as liver problems, low white blood cell count, and fluid retention.

Overall, these treatments have undergone extensive study. While they can cause some side effects, they are generally considered safe for people with head and neck cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment approach for head and neck cancer because it combines immunotherapy with chemotherapy to enhance the body's natural defenses against cancer cells. Unlike standard treatments that often rely solely on chemotherapy, this regimen includes Pembrolizumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells more effectively. This combination has the potential to improve outcomes by both shrinking tumors before surgery and reducing the risk of recurrence afterward. By using a multi-faceted approach, researchers hope to achieve better results than with traditional chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that using pembrolizumab with chemotherapy can help treat head and neck squamous cell carcinoma (HNSCC). In this trial, participants will receive pembrolizumab along with chemotherapy drugs like cisplatin (or carboplatin) and docetaxel before surgery, and pembrolizumab will continue after surgery. Studies have found that pembrolizumab, given before and after surgery, helps patients with locally advanced cases live longer without the cancer returning. When combined with chemotherapy drugs like cisplatin, patients with advanced HNSCC have lived longer than with standard treatments. Cisplatin and carboplatin are effective chemotherapy drugs for head and neck cancer, with cisplatin often being the preferred choice. Docetaxel, another chemotherapy drug, has also been effective in treating advanced or recurrent head and neck cancers. These findings suggest that this combination could be promising for those with surgically removable head and neck cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Kartik Sehgal

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

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 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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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, 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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9470832/

Effectiveness of paclitaxel and carboplatin combination in ... Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... With a median follow-up of 69 months for surviving patients, the 5-year progression-free survival was 36% and the 5-year overall survival was 35%. Two of the 18 ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41203-9/fulltext

Long-term outcomes with concurrent carboplatin, paclitaxel ... Treatment with concurrent carboplatin, paclitaxel and radiation is safe and offers curative potential for poor prognosis patients with locally advanced SCCHN.

4. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/617689

Carboplatin: The Better Platinum in Head and Neck Cancer? Among the 52 patients who completed the study, there were 17 complete responses (33%), 28 partial responses (54%), five patients with no change (10%), and two ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655522004551

Efficacy and Tolerance of Carboplatin plus Cetuximab ... Median overall survival was 10.1 months in patients with performance status 0–1. •. Patients with grade 1 or more skin toxicity had a higher ORR and a prolonged ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9773311/

Safety and preliminary activity of pembrolizumab-carboplatin ... In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6853181/

Definitive Chemoradiotherapy With Carboplatin for ... Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT ...

8. academic.oup.com academic.oup.com/jjco/article/45/12/1116/2384964

Safety and efficacy of concurrent carboplatin plus radiotherapy ... Concurrent carboplatin plus radiotherapy is tolerated and may be an option in treating locally advanced squamous cell carcinoma of the head and neck patients.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)43305-X/fulltext

Safety and efficacy of carboplatin, capecitabine plus ... Biweekly regimen is comparable and safe alternative first line regimen in R/M SCCHN patients. Evaluation of this regimen in prospective clinical trials is ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT00176267

Paclitaxel, Carboplatin And Low Dose Radiation As ... This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery ...