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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of combining quad-shot palliative radiotherapy with the immunotherapy drug pembrolizumab (also known as KEYTRUDA or MK-3475). The focus is on treating advanced, recurrent, or metastatic head and neck cancer that standard treatments cannot cure. Individuals with head and neck cancer that has recurred or spread and who need symptom relief might be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering patients a chance to contribute to significant advancements in cancer care.

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.

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

Research has shown that quad-shot palliative radiotherapy with pembrolizumab has been studied for safety in treating advanced head and neck cancer. Studies have found that quad-shot radiotherapy is generally safe and well-tolerated. Patients may experience some side effects, but these are usually manageable.

Pembrolizumab, an FDA-approved immunotherapy for other cancers, has a well-known safety profile. When combined with quad-shot radiotherapy, research suggests it remains safe for most patients. Common side effects might include tiredness and skin reactions, but these are usually mild.

Overall, existing research has demonstrated that both treatments are safe when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining pembrolizumab with quad-shot palliative radiotherapy for head and neck cancer because it offers a fresh approach by pairing immunotherapy with a unique radiotherapy schedule. Pembrolizumab works by unleashing the immune system to target cancer cells, which is different from traditional chemotherapy that directly attacks the cells. The quad-shot radiotherapy is administered in a shorter, more intensive burst, potentially reducing side effects and improving patient comfort compared to the longer durations of standard radiotherapy. This innovative combination aims to enhance the overall effectiveness and tolerability of the treatment, providing new hope for patients with advanced head and neck cancer.

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

Research has shown that using pembrolizumab, a type of immunotherapy, along with quad-shot palliative radiotherapy, might help treat advanced head and neck cancer. Participants in this trial will receive this combination treatment. Studies have found that this combination can be safe and may help manage symptoms for patients with this cancer. Pembrolizumab boosts the immune system to fight cancer cells, while quad-shot radiotherapy uses targeted, low-dose radiation to shrink tumors. Early results suggest that this combination can improve patient outcomes, making it a promising treatment option for those in advanced stages of the disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Mercedes Porosnicu

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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.

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37199326/

quad-shot radiotherapy with pembrolizumab for advanced ... We aim to test the effectiveness of an immunotherapy drug called pembrolizumab in combination with a type of low-dose radiation therapy called quad-shot.

2. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2022-1146

quad-shot radiotherapy with pembrolizumab for advanced/ ... We aim to test the effectiveness of an immunotherapy drug called pembrolizumab in combination with a type of low-dose radiation therapy called quad-shot.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04373642

Study Details | NCT04373642 | "QUAD SHOT" ... The purpose of this study is to test the safety of palliative "QUAD SHOT" radiotherapy combined with pembrolizumab and evaluate the effects of the combination ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-07332

Quad-Shot Radiation Therapy in Combination with ... This phase II trial studies how well quad-shot radiation therapy works in combination with pembrolizumab in treating head and neck cancer.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825001041

Palliative expeditiously adaptive quad shot radiotherapy for ... Quad shot is a safe and effective treatment for advanced head and neck cancer. •. Additional appointments between cycles can be onerous for this patient ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463211/

quad-shot radiotherapy with pembrolizumab for advanced ... Response rates in published studies of quad-shot palliative radiotherapy for head and neck cancer. Study, Dose, Gy/number of fractions, Response ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12284596/

Palliative expeditiously adaptive quad shot radiotherapy for ... Quad shot is a safe and effective treatment for advanced head and neck cancer. Additional appointments between cycles can be onerous for ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04373642/

Clinical Trial: NCT04373642 The purpose of this study is to test the safety of palliative "QUAD SHOT" radiotherapy combined with pembrolizumab and evaluate the effects ...