Personalized Radiotherapy for Head and Neck Cancer

(PULS-Pal Trial)

Overseen By Mili Santoso

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Pregnant, Breast-feeding, Prior radiation, others

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

Compensation: Varies

Number of Visits: 5

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage symptoms and control tumors in people with head and neck cancer, particularly those unable or unwilling to undergo standard treatments. It combines Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR), which delivers larger radiation doses less frequently, with HyperArc, a technology that targets the tumor while protecting healthy tissue. The aim is to provide more effective treatment with fewer side effects. Individuals with head and neck cancer who have measurable disease and have either opted out of or cannot receive standard treatments might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatments not available elsewhere.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this personalized radiotherapy technique is safe for head and neck cancer patients?

Research shows that PULSAR, combined with HyperArc technology, is under evaluation for safety and effectiveness in treating head and neck cancer. Earlier studies indicate that patients have generally tolerated PULSAR well. This approach uses larger doses of radiation in fewer sessions, aiming to target cancer cells more precisely while protecting healthy tissue.

HyperArc planning technology reduces exposure to nearby healthy organs, potentially lowering the risk of side effects. Although detailed safety data for this combination is still under review, the goal is to control tumors with fewer or similar side effects compared to standard radiation treatments. It is important to note that PULSAR and HyperArc together are still being studied to confirm these expectations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for head and neck cancer—which often involves conventional radiation therapy—Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) stands out with its tailored approach. Researchers are excited because PULSAR uses advanced imaging and HyperArc software to customize radiation doses specifically for each patient, potentially enhancing precision and reducing side effects. This technique also involves delivering higher doses of radiation in fewer sessions, which could make treatment more convenient and possibly more effective. By adapting the treatment based on ongoing assessments like PET scans and MRIs, PULSAR aims to optimize outcomes and personalize care in ways that traditional methods can't match.

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

Research has shown that using PULSAR, a type of personalized, precise radiation therapy, with HyperArc technology may help control tumors in head and neck cancer. In this trial, participants will receive PULSAR, which delivers larger, focused doses of radiation that adjust to changes in the tumor, potentially leading to better results. Studies have found that combining PULSAR with HyperArc allows for higher doses to the tumor while protecting nearby healthy tissues. This combination effectively relieved symptoms and controlled tumor growth in previous patients. Early findings suggest that this approach could be a safe and effective option for managing head and neck cancer when standard treatments are not suitable. ^{1 2 3 6 7}

Who Is on the Research Team?

Travis Courtney, MD

Principal Investigator

University of California at Los Angeles

Are You a Good Fit for This Trial?

This trial is for patients with primary or recurrent head and neck cancer who can't have or don't want standard treatments. It's focused on palliative care, aiming to control symptoms and pain rather than cure the disease.

Inclusion Criteria

I have a tracheostomy or a feeding tube and can join the study.

I have a tumor in my head or neck that can be measured.

I have been diagnosed with head and neck cancer at any stage.

Exclusion Criteria

Any comorbidity or condition which would limit full compliance with the protocol

I've had more than one radiation treatment in the same area or finished my last one over 6 months ago.

Pregnant or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive PULSAR fraction therapy using HyperArc technology for palliative treatment of head and neck cancer

8 weeks

5 visits (in-person) on days 0, 14, 28, 42, and 56

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Periodic visits, including possible PET scan and MRI

What Are the Treatments Tested in This Trial?

Interventions

• Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy

Trial Overview Researchers are testing a combination of personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) with HyperArc technology. They hope this will deliver higher doses of radiation more effectively to tumors with fewer side effects.

How Is the Trial Designed?

Group I: Treatment (PULSAR and HyperArc) Experimental Treatment 8 Interventions

Patients undergo standard of care CT simulation for radiation treatment planning using HyperArc software. 1 week later, patients undergo PULSAR fraction therapy once daily on days 0, 14, 28, 42, and 56. Patients may also undergo Positron Emission Tomography (PET) scan and MRI during follow-up.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

In a study of 302 patients with advanced head and neck cancer, delivering a minimum dose of 57.6 Gy of postoperative radiotherapy significantly reduced the risk of local-regional recurrence compared to doses of 54 Gy or lower.

For patients with extracapsular nodal disease, a boost to 63 Gy was necessary to lower recurrence rates, while escalating the dose above 63 Gy did not provide additional benefits and was associated with increased complications in 7.1% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Peters, LJ., Goepfert, H., Ang, KK., et al.[2022]

The HARDWINS treatment for advanced head and neck cancer, involving radiation dose escalation up to 64Gy, was delivered safely without any grade 4 acute toxicity, although significant grade 3 toxicity was observed, particularly affecting the pharynx and esophagus.

With a 5-year overall survival rate of 65% and a relapse-free rate of 63%, HARDWINS shows promising outcomes as an alternative to chemoradiation, despite a notable incidence of feeding tube dependence in patients receiving the highest radiation dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer. Waldron, J., Warde, P., Irish, J., et al.[2018]

Onboard volumetric imaging systems during head and neck radiotherapy allow for precise monitoring of patient anatomy, enabling the assessment of delivered doses and the impact of daily positioning and anatomical changes.

Adaptive radiotherapy aims to adjust treatment plans based on individual patient variations, but the effectiveness and clinical benefits of these adaptive strategies, particularly the use of deformable image registration algorithms, need further validation before widespread implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Head and neck adaptive radiotherapy]. Graff, P., Huger, S., Kirby, N., et al.[2013]

In a study of 918 patients with advanced head and neck squamous cell carcinomas, continuous hyperfractionated accelerated radiotherapy (CHART) showed similar long-term survival outcomes compared to conventional radiotherapy (CRT), despite using a lower total radiation dose (54 Gy vs. 66 Gy).

CHART was associated with a significantly lower incidence of severe late adverse events, such as xerostomia and laryngeal edema, making it a safer treatment option for patients with low-risk disease or those who cannot tolerate the side effects of concurrent chemoradiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mature results of a randomized trial of accelerated hyperfractionated versus conventional radiotherapy in head-and-neck cancer. Saunders, MI., Rojas, AM., Parmar, MK., et al.[2022]

Current head and neck intensity-modulated radiotherapy (IMRT) can cause significant toxicity due to its inability to adapt to daily changes in tumor and normal tissue locations, which may lead to unintended exposure of healthy tissues to high radiation doses.

Adaptive radiotherapy (ART) offers a promising solution by allowing for modifications to treatment plans based on daily anatomical changes, and initial clinical findings suggest it could improve treatment safety and efficacy, although technical challenges remain for its routine implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiation therapy for head and neck cancer-can an old goal evolve into a new standard? Schwartz, DL., Dong, L.[2021]

A study of 110 head and neck cancer patients developed an efficient strategy to identify candidates for adaptive radiotherapy (ART) within the first two weeks of treatment, focusing on the changes in dose to organs at risk (OARs).

The proposed selection strategy demonstrated high sensitivity and specificity for predicting patients at risk of significant toxicity, with the best results showing a 92% sensitivity for acute toxicity and 100% for late toxicity, indicating its potential to optimize ART use effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An efficient strategy to select head and neck cancer patients for adaptive radiotherapy. Gan, Y., Langendijk, JA., van der Schaaf, A., et al.[2023]

In a study of 155 head and neck cancer patients undergoing radiation therapy, it was found that dysphagia (difficulty swallowing) symptoms were strongly linked to the radiation dose delivered to the pharyngeal constrictor muscles, with higher doses correlating to worse symptoms.

Adaptive radiation therapy (ART) that focuses on reducing dysphagia may significantly lower the risk of these symptoms post-treatment, suggesting a new direction for ART that could improve patient outcomes beyond just reducing dry mouth (xerostomia).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes-Guided Adaptive Radiation Therapy for Head and Neck Cancer. Weppler, S., Quon, H., Schinkel, C., et al.[2022]

Adaptive radiotherapy for head and neck cancer significantly improved tumor coverage and reduced radiation exposure to critical organs, such as the spinal cord and parotid glands, leading to better dosimetric outcomes.

The study found a strong correlation between tumor volume reduction during treatment and patient survival, with those achieving greater than 35.2% tumor volume reduction experiencing significantly longer disease-free survival (16.9 months) compared to those with lower reductions (8.7 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Radiotherapy for Head and Neck Cancer. Surucu, M., Shah, KK., Roeske, JC., et al.[2018]

In a study of 34 patients with locally advanced head and neck cancer, significant volumetric changes were observed in target volumes during adaptive radiotherapy, indicating the need for mid-treatment replanning to optimize treatment effectiveness.

Despite the labor-intensive nature of adaptive replanning, the study found that dosimetric changes in organs at risk were not significant, suggesting that while target volumes change, the safety of surrounding healthy tissues may be maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer: A prospective study. Chophy, A., Gupta, S., Singh, P., et al.[2023]

The novel Adapt-To-Shape-Lite (ATS-Lite) strategy for adaptive radiotherapy in head and neck cancer patients achieved an impressive 99.9% compliance with mandatory dose constraints, outperforming traditional Adapt-To-Position (ATP) methods which failed 7.6% of the time.

ATS-Lite demonstrated efficient treatment delivery times, with median fraction times of approximately 40 minutes and 32 minutes for two patients, making it a practical option for patient care while maintaining high clinical standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online adaptive radiotherapy for head and neck cancers on the MR linear Accelerator: Introducing a novel modified Adapt-to-Shape approach. Gupta, A., Dunlop, A., Mitchell, A., et al.[2022]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(25)02856-1/fulltext

Personalized Ultrafractionated Stereotactic Adaptive ... We seek to evaluate a new head and neck cancer palliative radiotherapy regimen. ... Outcomes data for the combination of PULSAR and systemic therapy ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625028561

2729 Personalized Ultrafractionated Stereotactic Adaptive ... We seek to evaluate a new head and neck cancer palliative radiotherapy regimen. ... Outcomes data for the combination of PULSAR and systemic therapy ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-13303-5

A phase II study of personalized ultrafractionated stereotactic ... This single-arm phase II study will prospectively evaluate PULSAR with HyperArc© software for palliative treatment of head and neck cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12369228/

Use of PULSAR (personalized ultra-fractionated stereotactic ... We present a case of extensive and bulky pediatric metastatic melanoma originating in the head and neck which markedly responded to combination ...

5. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/trial/NCT06572423

University of California Health Head and Neck Cancer Trial This trial tests how well personalized ultra fractionated stereotactic adaptive radiotherapy (PULSAR) works together with HyperArc© radiation treatment ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39709372/

a single-arm clinical trial protocol A phase II study of personalized ultrafractionated stereotactic adaptive radiotherapy for palliative head and neck cancer treatment (PULS-Pal): ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/530575

Personalized Ultrafractionated Stereotactic Adaptive ... This trial tests how well personalized ultra fractionated stereotactic adaptive radiotherapy (PULSAR) works together with HyperArc© ...