Proton Therapy + Pembrolizumab for Head and Neck Cancer

Overseen By UCCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Cincinnati

Must not be taking: PD-1 inhibitors, Steroids

Disqualifiers: Metastatic disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether specific types of radiation therapy before surgery and immunotherapy (which uses the body's immune system to fight cancer) can benefit individuals with a certain type of head and neck cancer. The focus is on recurrent squamous cell carcinoma in areas like the mouth or throat. Participants must have experienced a recurrence of this cancer after previous radiation treatment and plan to undergo surgery to remove it. The trial compares standard radiation with a newer method called proton therapy to determine which is more effective at shrinking tumors before surgery and immunotherapy. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 investigational agents or high-dose steroids, you may not be eligible. 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 proton therapy is generally safe for treating head and neck cancer. Studies have found that it often leads to better survival rates and fewer side effects compared to traditional radiation treatments. For example, one study found that patients who received proton therapy lived longer and experienced fewer local issues than those who received other types of radiation.

Another study involving over 60,000 patients with head and neck cancer found that proton therapy was associated with better survival rates and fewer side effects in nearby areas. This suggests that proton therapy might be a well-tolerated option for patients.

Prospective participants in a clinical trial for proton therapy should discuss potential benefits and risks with their healthcare provider, considering their personal health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to fighting head and neck cancer. Unlike the standard radiation therapy that uses X-rays, proton therapy precisely targets tumors with less damage to surrounding healthy tissue. This precision could mean fewer side effects and potentially better outcomes for patients. Additionally, when combined with pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, there might be an enhanced anti-cancer effect. This combination aims to leverage the accuracy of proton therapy and the immune-boosting power of pembrolizumab for a more effective treatment option.

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

In this trial, participants will receive either standard radiation therapy or photon therapy, a form of proton therapy. Studies have shown that proton therapy holds promise for treating head and neck cancers, often causing fewer issues in healthy tissues than regular radiation. Specifically, research involving 60,485 patients with head and neck squamous cell carcinoma (HNSCC) found that proton therapy led to better overall survival rates and reduced recurrence in the treated area. Patients experienced similar cancer control but with fewer side effects and improved quality of life compared to traditional methods. These findings suggest that proton therapy could be a more effective and gentler treatment option for head and neck cancer patients. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent head and neck squamous cell carcinoma (rHNSCC) who are candidates for surgery. Specific eligibility criteria details were not provided, so interested participants should inquire further to determine if they qualify.

Inclusion Criteria

Women of child-bearing potential and men must agree to use adequate contraception. Women should inform their treating physician immediately if pregnant or suspect pregnancy.

I am 18 years old or older.

My cancer is a type of squamous cell carcinoma in the head or neck area.

Exclusion Criteria

Patients with ongoing adverse events from prior anti-cancer therapy that would preclude completion of the proposed study treatment at the opinion of the treating investigators.

Patients receiving any other investigational agents. Patients who have received other investigational agents previously may be eligible at the discretion of the PI.

Autoimmune disease or other pro-inflammatory conditions other than treated stable asthma, minor allergies, vitiligo, or hypothyroidism.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive X-ray photon radiation (XRT) or proton radiation (PT) prior to surgery

3 fractions

Multiple visits for radiation sessions

Surgery

Participants undergo surgical salvage after radiation therapy

1 week

Immunotherapy

Participants receive PD-1 inhibition (pembrolizumab) following surgery

Cycle length is 21 days

Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Proton Therapy

Trial Overview The study is testing the safety of combining X-ray photon radiation or proton radiation with pembrolizumab immunotherapy before surgery in patients with rHNSCC. It's a two-part study: Phase I checks for safety, while Phase II evaluates the treatment's benefits.

How Is the Trial Designed?

Group I: Photon Therapy Experimental Treatment 2 Interventions

PT followed by PD-1 inhibition

Group II: Standard Radiation Therapy Active Control 1 Intervention

XRT followed by PD-1 inhibition

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11579081/

Proton Therapy in The Treatment of Head And Neck Cancers Proton therapy represents a promising alternative to conventional radiotherapy due to the reduced number of complications in healthy tissues.

2. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/imrt-matches-proton-therapy-in-patient-reported-outcomes-for

Intensity-modulated radiation therapy (IMRT) matches ... At a median follow-up of 28.3 months, two-year freedom from cancer returning at or near the original tumor site was 94.3% for protons and 96.8% ...

3. mskcc.org mskcc.org/clinical-updates/proton-beam-reduces-acute-toxicities-compared-to-imrt-for-head-and-neck-cancer-patients-who-receive-unilateral-radiation

Proton Beam Reduces Acute Toxicities Compared to IMRT ... Proton beam radiotherapy resulted in similar oncologic outcomes with less toxicity and improved quality of life than photon beam ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814023898656

Comparing the oncologic outcomes of proton therapy and ... This study of 60,485 patients with HNSCC found that proton therapy was associated with better overall and cancer-specific survival and lower locoregional ...

5. mdanderson.org mdanderson.org/newsroom/asco--proton-therapy-demonstrates-advantages-in-phase-iii-head-a.h00-159698334.html

ASCO: Proton therapy demonstrates advantages in Phase ... With a median follow-up of three years, the progression-free survival (PFS) rate was 83% and 83.5% for IMPT and IMRT, respectively, and IMPT was ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39007360/

Efficacy and safety of proton therapy versus intensity ... Proton therapy demonstrated superior overall survival (OS), disease-free survival (DFS), and better local control rate (LCR) compared to IMRT.

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2798320

Toxicity Profiles and Survival Outcomes Among Patients ... This cohort study compares the toxic effects and oncologic outcomes associated with intensity-modulated radiation therapy (IMRT) vs ...

8. redjournal.org redjournal.org/article/S0360-3016(25)02926-8/fulltext

Evaluation of Efficacy and Safety of Proton Reirradiation in ... We reviewed 84 cases of proton re-irradiation done at our facility to explore toxicity profiles and survival data. There was a high recurrence rate with over 63 ...