Proton Therapy for Head and Neck Cancer

Recruiting at 9 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Immunocompromised, Active infection, Cardiac issues, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 3-4 weeks

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of radiation therapies to evaluate their effectiveness after surgery for head and neck cancer. One treatment uses proton therapy (Intensity-Modulated Proton Therapy) to aim radiation precisely, reducing side effects. The other uses X-ray radiation to target the tumor from multiple angles, sparing nearby healthy tissue. The study compares the effectiveness of these treatments, sometimes with the addition of a standard chemotherapy drug called cisplatin. Individuals with head and neck cancer not related to HPV who have undergone 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 of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research shows that Intensity-Modulated Proton Therapy (IMPT) is generally easy for patients to handle. Studies have found that proton therapy often causes fewer side effects than traditional radiation treatments. For example, patients experience fewer moderate side effects with proton therapy, meaning they usually feel better during treatment.

When comparing Intensity-Modulated X-ray Therapy (IMRT) to proton therapy, studies have found no major differences in long-term side effects or quality of life. This indicates that both treatments are safe and have similar results for patients over time.

Cisplatin, a chemotherapy drug used with these therapies, is well-known and commonly used. Healthcare providers understand and manage its side effects effectively.

Overall, both IMPT and IMRT are safe options for treating head and neck cancer, with proton therapy possibly offering a slight advantage in reducing some immediate side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the trial for intensity-modulated proton therapy (IMPT) for head and neck cancer because it offers a unique approach compared to traditional radiation methods like intensity-modulated radiation therapy (IMRT). IMPT precisely targets tumors with proton beams, potentially reducing damage to surrounding healthy tissue and lessening side effects. This precision is especially beneficial for head and neck cancer, where nearby vital structures can be affected by radiation. Additionally, the trial incorporates the use of cisplatin, a chemotherapy drug, to enhance the effectiveness of the radiation therapy. By combining these advanced techniques, researchers hope to achieve improved outcomes and better quality of life for patients.

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

This trial will compare different treatment approaches for head and neck cancer. Participants may receive intensity-modulated proton therapy (IMPT), which studies have shown to be very effective for this type of cancer. Research indicates that proton therapy offers better survival rates and reduces the likelihood of cancer recurrence compared to intensity-modulated X-ray therapy (IMRT). Proton therapy also controls cancer more effectively in the targeted area, potentially preventing its return. The main advantage of IMPT is its precision, allowing it to target tumors more accurately with less harm to nearby healthy tissue. This precision can lead to fewer side effects compared to traditional radiation methods like IMRT. Both IMPT and IMRT are promising, but IMPT might offer additional benefits in terms of treatment effectiveness and reducing side effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Scott C. Lester, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with non-HPV head and neck cancers, including oral, paranasal sinus, salivary gland, skin cancer, etc., who have good blood counts and organ function. They must be COVID-19 negative or recovered and not immunocompromised (except stable HIV). Pregnant women and those with recent heart issues or other active cancers are excluded.

Inclusion Criteria

My cancer is in my head or neck area, including the mouth and throat.

My scans show no signs of cancer spread beyond its original site.

My cancer in the head or neck is not related to HPV.

Exclusion Criteria

I have not had any other cancer within the last 2 years.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Pregnant women (serum pregnancy test required before treatment per department policy)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients undergo IMPT or IMRT for 15-18 sessions over 19-24 days, with optional cisplatin administration

3-4 weeks

15-18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Regular visits at months 3, 6, 9, 12, 15, 18, 24, 35, 48, and 60

Long-term Follow-up

Monitoring of long-term outcomes such as survival and recurrence rates

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Intensity-Modulated Proton Therapy

Trial Overview The trial is testing intensity-modulated proton therapy as a post-surgery treatment to reduce tumor size in patients with various types of head and neck cancer. It includes cisplatin chemotherapy alongside radiation therapy using high-energy protons.

How Is the Trial Designed?

Group I: Arm C (IMRT, cisplatin) Experimental Treatment 8 Interventions

Patients undergo IMRT for 15 sessions over 19 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care. Patients undergo CT or MRI and PET/CT or PET/MRI during screening and follow-up. Patients may also undergo blood sample collection throughout the trial.

Group II: Arm B (IMPT, cisplatin) Experimental Treatment 8 Interventions

Patients undergo IMPT for 15 sessions over 19 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care. Patients undergo CT or MRI and PET/CT or PET/MRI during screening and follow-up. Patients may also undergo blood sample collection throughout the trial.

Group III: Arm A (IMPT, IMRT, cisplatin) Experimental Treatment 9 Interventions

Patients undergo IMPT or IMRT for 18 sessions over 24 days in the absence of disease progression or unacceptable toxicity. Patients may receive cisplatin IV over 1-2 hours per standard of care. Patients undergo CT or MRI and PET/CT or PET/MRI during screening and follow-up. Patients may also undergo blood sample collection throughout the trial.

Intensity-Modulated Proton Therapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as IMPT for:

• Head and neck cancers
• Squamous cell carcinoma
• Nasopharyngeal cancer
• Oropharyngeal cancer
• Thyroid cancer
• Salivary gland cancer

Approved in European Union as IMPT for:

• Head and neck cancers
• Squamous cell carcinoma
• Nasopharyngeal cancer
• Oropharyngeal cancer
• Thyroid cancer
• Salivary gland cancer

Approved in Canada as IMPT for:

• Head and neck cancers
• Squamous cell carcinoma
• Nasopharyngeal cancer
• Oropharyngeal cancer
• Thyroid cancer
• Salivary gland cancer

Approved in Japan as IMPT for:

• Head and neck cancers
• Squamous cell carcinoma
• Nasopharyngeal cancer
• Oropharyngeal cancer
• Thyroid cancer
• Salivary gland cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intensity-modulated proton therapy (IMPT) offers significant dosimetric advantages over traditional photon radiation therapy, allowing for higher doses to be delivered to tumors while sparing critical surrounding organs, which may lead to reduced toxicity.

Existing evidence suggests that IMPT can improve patient-reported outcomes, reduce malnutrition, and decrease the need for gastrostomy tubes in patients with head and neck cancers, highlighting its potential benefits in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced acute toxicity and improved efficacy from intensity-modulated proton therapy (IMPT) for the management of head and neck cancer. McKeever, MR., Sio, TT., Gunn, GB., et al.[2017]

Intensity-modulated proton therapy (IMPT) shows promise in treating HPV-associated oropharyngeal squamous cell carcinoma (OPC) by reducing side effects while maintaining effective treatment for the tumor, as it spares normal tissues from high radiation doses.

Retrospective studies indicate that IMPT results in lower rates of complications such as pain, dry mouth, and difficulty swallowing compared to traditional X-ray radiotherapy, which can significantly improve the quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy. Taku, N., Wang, L., Garden, AS., et al.[2022]

Intensity-modulated proton therapy (IMPT) for oropharyngeal carcinoma shows a potential reduction in severe weight loss and feeding tube dependency compared to intensity-modulated radiotherapy (IMRT), based on a study of 150 matched patients with a median follow-up of 32 months.

Despite these benefits, there were no significant differences in overall survival or progression-free survival between IMPT and IMRT, indicating that IMPT does not compromise treatment effectiveness while potentially improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis. Blanchard, P., Garden, AS., Gunn, GB., et al.[2022]

Intensity-modulated proton therapy (IMPT) significantly reduced the radiation dose to the parotid glands compared to both intensity-modulated radiotherapy with photons (IMRT) and three-dimensional conformal radiotherapy (3D-CRT), suggesting a potential for less salivary dysfunction and xerostomia in patients with oropharyngeal cancer.

While IMPT and IMRT provided similar coverage of the target areas, IMPT showed improved conformity in sparing surrounding healthy tissues, indicating a theoretical clinical benefit that needs further validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential benefits of scanned intensity-modulated proton therapy versus advanced photon therapy with regard to sparing of the salivary glands in oropharyngeal cancer. van de Water, TA., Lomax, AJ., Bijl, HP., et al.[2018]

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

Intensity modulated proton therapy (IMPT) shows significant dosimetric advantages over traditional intensity modulated radiation therapy (IMRT) for head and neck cancers, particularly in sparing nearby organs like the larynx and salivary glands.

Clinical evidence suggests that IMPT can reduce treatment-related toxicities, such as the need for feeding tubes, indicating its potential benefits in improving patient quality of life during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer. Moreno, AC., Frank, SJ., Garden, AS., et al.[2020]

Intensity modulated proton beam therapy (IMPT) significantly reduces the average radiation dose to tooth-bearing regions in head and neck cancer patients compared to photon-based volumetric modulated arc therapy (VMAT), indicating a safer option for preserving dental health during treatment.

In a study of 121 patients, factors such as oral cavity tumors and advanced T3-T4 tumors were identified as risk factors for receiving a cumulative radiation dose of ≥40 Gy to tooth-bearing areas, which is critical for determining the need for prophylactic dental extractions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions. Alberga, JM., Meijer, J., Raghoebar, GM., et al.[2023]

Citations

1. 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% ...

2. 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.

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

Comparing the oncologic outcomes of proton therapy and ... Proton therapy is associated with superior outcomes in terms of overall survival, cancer-specific survival, and locoregional recurrence rates compared to IMRT ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6615027/

Intensity Modulated Proton Therapy (IMPT) – The Future of ... Puri DR, Chou W, Lee N. Intensity-modulated radiation therapy in head and neck cancers: dosimetric advantages and update of clinical results.

5. tro.amegroups.org tro.amegroups.org/article/view/7610/html

A narrative review of intensity-modulated proton therapy for ... IMPT is more advantageous than PSPT in treating head and neck cancer due to the increased flexibility in targeting complex, irregularly shaped ...

6. 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 ... Proton therapy achieved similar clinical outcomes while reducing malnutrition and feeding-tube dependency compared with traditional radiation therapy.