Radiotherapy + Immunotherapy for Head and Neck Cancer

Overseen By Study Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Pregnancy, Autoimmune disease, Organ transplant, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have used certain cancer treatments or immunosuppressive medications within the last 30 days. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Pembrolizumab combined with Quad-shot radiotherapy for head and neck cancer?

Research shows that Pembrolizumab, an immune therapy drug, has shown modest response rates in advanced head and neck cancer. When combined with Quad-shot radiotherapy, which helps control symptoms and may enhance immune response, it could potentially improve outcomes for patients with advanced or recurrent head and neck cancer. ^{1 2 3 4 5}

Is the combination of radiotherapy and pembrolizumab safe for treating head and neck cancer?

Pembrolizumab, used in combination with radiotherapy, has been evaluated for safety in patients with head and neck cancer. Common serious side effects include pneumonia, breathing difficulties, confusion, vomiting, and respiratory failure. Some patients also experienced immune-related side effects like lung inflammation, liver inflammation, and thyroid issues, but the overall safety profile was considered acceptable for this patient group. ^{2 3 4 5 6}

How is the treatment of radiotherapy combined with pembrolizumab unique for head and neck cancer?

This treatment is unique because it combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with a special type of radiotherapy called 'quad-shot', which is given in short, intense bursts to relieve symptoms and enhance the immune response. This approach is particularly useful for patients with advanced or recurrent head and neck cancer who have limited treatment options. ^{1 3 4 5 7}

Research Team

Mercedes Porosnicu

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

Adults with advanced, recurrent, or metastatic head and neck squamous cell carcinoma suitable for palliative radiotherapy. Participants must be over 18, have a performance status of 0-2 (able to carry out daily activities), agree to use contraception if applicable, and have adequate organ function. Exclusions include pregnancy, prior significant immunotherapy reactions, certain heart conditions, uncontrolled illnesses like hypertension or infections.

Inclusion Criteria

I am willing to give blood and saliva samples for research.

I agree to use effective birth control or abstain from sex during the study.

I can understand and am willing to sign the consent form.

Exclusion Criteria

Mean QT interval corrected for heart rate (QTc) ≥470 ms except for patients with pacemaker who have a paced ventricular rhythm

I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.

Participation in another clinical study with an investigational product during the last 3 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 3 weeks and undergo quad-shot radiation therapy twice daily on 2 consecutive days between specific cycles of pembrolizumab treatment.

Up to 2 years

Follow-up

Participants are monitored for adverse events and survival endpoints after completion of study treatment.

2 months

Follow-up visits at 1 and 2 months

Long-term Follow-up

Participants are followed until death for monitoring survival study endpoints.

Treatment Details

Interventions

• Pembrolizumab
• Quad-shot palliative radiotherapy

Trial Overview The trial is testing the combination of quad-shot palliative radiotherapy with Pembrolizumab (an immunotherapy drug) in patients with advanced head and neck cancer. It's a single-arm study where all participants receive both treatments to assess effectiveness and side effects.

Participant Groups

Group I: Quad-shot palliative radiotherapy and Immunotherapy Experimental Treatment 2 Interventions

Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., 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 study investigates the combination of the immune checkpoint inhibitor pembrolizumab with a hypofractionated palliative radiotherapy regimen called quad-shot in 15 patients with advanced/recurrent head and neck squamous-cell carcinoma, aiming to enhance treatment efficacy and provide symptomatic relief.

Outcomes will assess disease response, survival, and treatment toxicity, while also exploring molecular biomarkers through multiomics analysis to understand the immune response to the combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quad-shot-immunotherapy: quad-shot radiotherapy with pembrolizumab for advanced/recurrent head and neck cancer. Hughes, RT., Gebeyehu, RR., Kalada, JM., et al.[2023]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study of 21 patients with advanced head and neck cancer, the QUAD-Shot hypofractionated radiotherapy regimen combined with chemotherapy resulted in an 85.7% objective response rate, with 23.8% achieving complete response and 61.9% showing partial response.

All patients who completed the treatment experienced symptom relief, and the median overall survival was 7 months, indicating that this treatment is both effective and well-tolerated for patients not eligible for curative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen". Gamez, ME., Agarwal, M., Hu, KS., et al.[2019]

References

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

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [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

Quad-shot-immunotherapy: quad-shot radiotherapy with pembrolizumab for advanced/recurrent head and neck cancer. [2023]

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

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

6. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]

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

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen". [2019]