Shortened Adjuvant Radiotherapy for Throat Cancer

Recruiting at 3 trial locations

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: T4 disease, Metastatic, 5+ lymph nodes, others

Stay on Your Current Meds You can continue your current medications while participating

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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a shorter course of adjuvant radiotherapy (radiation therapy) is safe for individuals with HPV-linked throat cancer. Researchers aim to determine if reducing radiation doses after surgery can remain effective without affecting the main surgery area. This approach may suit those who have undergone throat cancer surgery with HPV-positive results and show no detectable cancer DNA in their blood post-surgery. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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 protocol is safe for HPV-Associated OPSCC patients?

Research shows that a shorter course of radiation therapy can be safe for patients with HPV-related throat cancer. Previous studies involved patients receiving a smaller total amount of radiation over a shorter period, which most handled well. For instance, one study tested giving half the usual radiation dose over two weeks instead of six weeks, and it showed promising safety results.

However, some patients in general radiation therapy settings stopped treatment due to side effects like radiation toxicity. While most manage the treatment well, some risks remain.

These findings suggest that shorter radiation treatment might be a safe option for some patients, but discussing personal risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the Shortened Course Adjuvant Radiotherapy for throat cancer because it significantly reduces the treatment time compared to traditional radiotherapy options. Most standard treatments for throat cancer involve higher doses over a longer period, often requiring several weeks of daily sessions. This new approach delivers a lower dose of 30 Gy over just 10 treatments, making it potentially less taxing for patients. Additionally, in certain cases, the treatment can skip the primary tumor bed if deemed appropriate, which aligns with efforts to reduce unnecessary exposure and side effects. This streamlined protocol could offer a more efficient and patient-friendly treatment option while maintaining effectiveness, sparking considerable interest among researchers.

What evidence suggests that this protocol is effective for throat cancer?

Earlier studies have shown that lowering the radiation dose for patients with HPV-related throat cancer reduces treatment side effects and improves quality of life. Research shows that less intense radiation effectively controls the cancer while decreasing severe and moderate side effects. Specifically, shorter radiation treatments have been linked to better overall survival and a lower chance of recurrence. This trial will evaluate a shortened course of adjuvant radiotherapy, which could offer a promising option for those with HPV-related throat cancer, balancing effectiveness with fewer side effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Alexander Lin, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific throat cancer (p16+ oropharyngeal squamous cell carcinoma) who've had surgery and some lymph node involvement but no distant spread of the disease. They must have good performance status, which means they can carry out daily activities without significant assistance.

Inclusion Criteria

I am over 18 years old.

Detectable preoperative plasma ctHPVDNA (copy number of more than 200 copies/mL)

Undetectable postoperative plasma ctHPVDNA

Exclusion Criteria

My cancer has spread to distant parts of my body.

I have had radiation therapy to my head or neck.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant radiotherapy following TORS and neck dissection, with a reduced dose of 30 Gy over 10 treatments

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Adjuvant Radiotherapy

Trial Overview The study tests if it's safe to give less radiation after transoral robotic surgery (TORS) and neck dissection in patients with certain throat cancers. It also explores whether avoiding radiation to the area where the tumor was removed is effective.

How Is the Trial Designed?

Group I: Shortened Course Adjuvant Radiotherapy Experimental Treatment 1 Intervention

The volume treated to the regional lymphatics will be according to the characteristics of the primary site and involved lymph nodes. The dose of radiotherapy delivered will be 30 Gy, over the course of 10 treatments (5 daily treatments/week). Treatment of the primary tumor bed will be omitted in appropriate patients, as per the initial TORS de-intensification protocol. In patients requiring treatment of the primary site, reduced dose (30 Gy) will be delivered.

Adjuvant Radiotherapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Radiotherapy for:

• Oropharyngeal squamous cell carcinoma (OPSCC)
• Head and neck cancers

Approved in United States as Radiation Therapy for:

• OPSCC
• Head and neck cancers
• Cervical cancer

Approved in Canada as Radiotherapy for:

• OPSCC
• Head and neck cancers

Approved in Japan as Radiotherapy for:

• OPSCC
• Head and neck cancers

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Published Research Related to This Trial

Laser phototherapy (LPT) significantly improved the quality of life for a 15-year-old girl undergoing radiotherapy for mucoepidermoid carcinoma, reducing pain and xerostomia after just a few sessions.

After 17 sessions of LPT, all oral mucositis lesions were eliminated, allowing the patient to regain normal oral function and enabling the use of a palatine plate for rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in quality of life of an oncological patient by laser phototherapy. Campos, L., Simões, A., Sá, PH., et al.[2015]

Curative radiotherapy for head and neck cancer leads to significant side effects that can greatly affect patients' quality of life and potentially impact the success of their treatment.

Effective management of these adverse effects is crucial to improve patient outcomes and enhance their overall treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing side effects of radiotherapy in head and neck cancer. Mendes, RL., Nutting, CM., Harrington, KJ.[2019]

In a study of 8795 patients with lymph node-positive head and neck cancer, adjuvant radiotherapy (RT) significantly improved 5-year overall survival rates (43.2% with RT vs 33.4% without RT) and cancer-specific survival (50.9% with RT vs 42.1% without RT).

Adjuvant RT was found to be a significant predictor of improved survival, with a hazards ratio of 0.78, indicating a 22% reduction in the risk of death, highlighting its efficacy in enhancing outcomes for patients with locally advanced squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy improves overall survival for patients with lymph node-positive head and neck squamous cell carcinoma. Lavaf, A., Genden, EM., Cesaretti, JA., et al.[2008]

External beam radiation therapy is a common and effective treatment for head and neck cancers, which account for about 3% of all cancers in the U.S., with 62,000 new cases diagnosed each year.

Due to the complex anatomy of the head and neck region, careful planning of radiation therapy is crucial to minimize side effects on critical structures, and the review provides guidelines for managing these side effects and improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Radiation Toxicity in Head and Neck Cancers. Siddiqui, F., Movsas, B.[2018]

A fast-track nutritional intervention for head and neck cancer patients undergoing radiotherapy led to significantly better nutritional status, with a lower prevalence of malnutrition (31.9% in the early group vs 69.5% in the conventional group).

Patients in the early intervention group required less nutritional support and experienced fewer emergency visits and hospitalizations three months after treatment, indicating improved overall health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early versus conventional nutritional intervention in head and neck cancer patients before radiotherapy: benefits of a fast-track circuit. González-Rodríguez, M., Villar-Taibo, R., Fernández-Pombo, A., et al.[2021]

In a study of 171 patients with head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy, those with prolonged radiation treatment times (over 7 weeks) faced a significantly higher risk of local tumor failure (hazard ratio of 2.6) and increased mortality (hazard ratio of 1.9).

These findings suggest that prolonged radiation treatment times can negatively impact tumor control and survival in patients receiving concurrent chemotherapy, highlighting the importance of managing symptoms effectively to avoid treatment delays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased local failure risk with prolonged radiation treatment time in head and neck cancer treated with concurrent chemotherapy. Cannon, DM., Geye, HM., Hartig, GK., et al.[2021]

The study developed the Functional Assessment of Cancer Therapy-Head and Neck Radiotherapy (FACT-HN-RAD) measure, an 8-item tool that effectively captures the most common adverse effects (AEs) of radiation therapy in patients with head and neck squamous cell carcinoma, based on input from 19 patients and 9 radiation oncologists.

Common AEs identified include difficulty swallowing, oral pain, dry mouth, and weight loss, with the measure demonstrating strong face validity among patients, indicating it accurately reflects their experiences during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Adverse Effects of Radiation Therapy in Patients With Head and Neck Cancer: The FACT-HN-RAD Patient-Reported Outcome Measure. Gharzai, LA., Mierzwa, ML., Peipert, JD., et al.[2023]

In a study of 30 patients undergoing radiotherapy for head and neck carcinomas, self-reported pain scores significantly increased from 35 in the first week to 151 by the final week, indicating that pain management is crucial as treatment progresses.

The rise in pain scores, particularly noted in week 3, suggests that radiation-induced inflammation and chemotherapy side effects contribute to increased discomfort, highlighting the need for individualized pain relief strategies and regular treatment reviews to maintain patient comfort and compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of self-reporting pain scores and pain management during head and neck IMRT radiotherapy: A single institution experience. O'Connor, P., Bisson, J., Asplin, P., et al.[2022]

Adjuvant radiotherapy (RT) significantly improves 5-year overall survival rates for patients with node-positive head and neck squamous cell carcinoma (HNSCC), with survival rates of 46.3% for surgery plus RT compared to 35.2% for surgery alone.

The benefits of adjuvant RT extend across all nodal stages (N1 to N3), with significant survival improvements noted for various primary tumor sites, indicating that RT is a crucial component of treatment for node-positive HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage. Kao, J., Lavaf, A., Teng, MS., et al.[2019]

In a study of 167 patients with oral cavity and oropharyngeal cancers, those who received whole-neck irradiation (WNI) had a significantly lower rate of cancer recurrence at neck level IV (2%) compared to those who underwent lower-neck-sparing (LNS) irradiation (10%).

The 2-year disease-free survival rates were higher in the WNI group (75%) compared to the LNS group (63%), indicating that WNI may be more effective in preventing recurrence and improving survival in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adjuvant radiotherapy in oral cavity or oropharyngeal cancer: Feasibility of omitting lower-neck irradiation. Ho, SY., Kao, WC., Hsiao, SY., et al.[2022]

Out of 324 head and neck squamous cell carcinoma patients undergoing radical radiotherapy, 76 (about 23.5%) discontinued treatment without medical authorization, indicating a significant issue with treatment compliance.

Factors contributing to non-compliance included financial difficulties (24.1%), preference for traditional healers (22.2%), and logistical challenges, particularly among patients living more than 100 km from the treatment center, highlighting the need for targeted support for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India. Pandey, KC., Revannasiddaiah, S., Pant, NK.[2020]

In a study of 60 patients with oropharyngeal carcinoma, those treated with radical radiotherapy (RT) reported better quality of life outcomes, particularly in speech, compared to those who underwent primary surgery followed by RT, especially in advanced-stage tumors (T3-4).

For patients with advanced-stage disease, radical RT not only showed superior functional outcomes but also suggested that if oncological results are similar, nonsurgical treatment may be the preferred option due to better quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life in patients with oropharynx carcinomas: assessment after accelerated radiotherapy with or without chemotherapy versus radical surgery and postoperative radiotherapy. Allal, AS., Nicoucar, K., Mach, N., et al.[2015]

In a phase 1 study involving 12 patients with resected head and neck squamous cell carcinoma, moderately hypofractionated radiation therapy (RT) was found to be well tolerated, with no dose-limiting toxicities reported.

The study determined that a dose of 44.4 Gy in 12 fractions was the maximum tolerated, but 46.5 Gy in 15 fractions was recommended for further testing due to better tolerability and equivalent effectiveness, indicating a promising approach to reduce treatment time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HYPORT: Phase 1 Study of 3-Week Hypofractionated Postoperative Radiation Therapy for Head and Neck Squamous Cell Carcinoma. Moon, DH., Avkshtol, V., Vo, D., et al.[2023]

The timing of radiotherapy (RT) is crucial for patients with advanced head and neck neoplasia, as factors like total treatment time and the length of adjuvant RT can significantly impact clinical outcomes.

Ensuring that there are no interruptions during RT is important, as these timing factors can serve as prognostic indicators, similar to tumor characteristics, affecting the effectiveness of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing factors as prognostic variables in patients with head and neck squamous cell carcinoma treated with adjuvant radiotherapy: a literature review. Franco, R., Marta, GN.[2020]

Citations

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Reduced-dose radiation in human papillomavirus ... Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients.

2. newsnetwork.mayoclinic.org newsnetwork.mayoclinic.org/discussion/shorter-less-intense-radiation-chemo-regimen-effective-for-hpv-linked-oropharyngeal-cancer-mayo-study-shows/

Shorter, less intense radiation-chemo regimen effective for ... The results demonstrated that the less intensive treatment approach significantly reduced both severe (grade 3 or higher) and moderate (grade 2) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1368837525002131

Benefit from adjuvant radiotherapy in early-stage oral ... Receipt of adjuvant RT was associated with improved OS (HR 0.49 [0.32; 0.76]) and a reduced risk of LRR (HR 0.39 [0.22; 0.69]. In addition, the analysis ...

4. practicalradonc.org practicalradonc.org/article/S1879-8500(24)00139-5/fulltext

Radiation Therapy for HPV-Positive Oropharyngeal ... The guideline focuses on the 3 main treatment modalities for OPSCC: RT, surgery, and systemic therapy. For systemic therapy recommendations, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0167814022002523

Characterization of clinical outcomes after shorter course ... Our data suggest that shorter hypo-RT regimens as adjuvant or definitive treatment are worthy of prospective evaluation, potentially as a multi-institutional ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5856974/

Premature discontinuation of curative radiation therapy The most common reasons for PDCRT were discontinuation against medical advice (33%), medical comorbidity (24%), and RT toxicity (17%).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02908477

Study Details | NCT02908477 | Evaluation of De-escalated ... This study investigates a less intense radiation treatment following surgery that uses half the dose of radiation given over two weeks rather than six weeks.

8. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)00252-3/fulltext

Characterization of clinical outcomes after shorter course ... Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2772906022000036

Adjuvant radiation vs Chemoradiation in HPV+ ... ENE (HR: 2.28) increased risk of death. In ENE ​+ ​cases, there was no difference in survival between CRT and RT cohorts following propensity score matching (P ...