Reduced Radiation Therapy for Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Heather Franklin, BSN, RN, OCN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Prior head/neck radiotherapy, Metastatic disease, others

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

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether people with certain types of throat cancer linked to HPV (a common virus) can safely receive less radiation during treatment. Researchers aim to determine if special scans during therapy, specifically 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT), can identify candidates for a lower radiation dose, potentially reducing side effects. Individuals with squamous cell carcinoma of the oropharynx who have tested positive for HPV and plan to start standard chemotherapy might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future cancer treatments.

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 patients with HPV-related oropharyngeal cancer?

Research has shown that lowering the radiation dose for HPV-related throat cancer might be safe for some patients. One study found that patients who received less radiation had a high survival rate, with over 96% still alive after two years, and most did not experience severe side effects. Another study reported that this approach led to good health outcomes and maintained a high quality of life. However, while some early studies were promising, later ones did not consistently show better results with lower doses. This indicates that findings vary, and safety depends on the specific situation. Patients should consult their doctor to determine if this approach is suitable for them. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial for reduced radiation therapy in treating oropharyngeal cancer because it explores the potential benefits of lowering radiation doses. Unlike standard high-dose radiation therapy, which can cause significant side effects, this approach aims to maintain effectiveness while reducing harm to healthy tissues. The trial uses interim PET-CT scans to guide the therapy, offering a more personalized treatment plan that could minimize unnecessary exposure. This technique might lead to fewer long-term side effects and improve the quality of life for patients.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that lower doses of radiation can effectively treat HPV-related throat cancer. In this trial, participants will be divided into two groups: one will receive an interim PET-CT with standard radiation, and the other will receive an interim PET-CT with dose de-escalation. Studies indicate that in patients with HPV-positive head and neck cancer, the cancer often shrinks early during treatment, which may allow for reduced radiation use. One study found that the survival rate after two years was very high for patients who received reduced radiation, similar to those who received standard doses. Another study noted that using less radiation led to fewer side effects while still achieving good results. Overall, evidence supports the effectiveness of lower radiation doses for treating HPV-related throat cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Jared Robbins, MD

Principal Investigator

DUHS

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HPV-related oropharyngeal cancer, confirmed by specific tests, who haven't had chemotherapy for their current diagnosis. They should be in good physical condition with minimal weight loss recently and have early to mid-stage cancer treatable with chemo.

Inclusion Criteria

I am fully active or can carry out light work.

I have lost less than 10% of my weight in the last 3 months.

My cancer is stage I-III and I will receive chemotherapy as standard care.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I have not had any cancer except for non-melanoma skin cancer in the past 5 years.

I have had radiation therapy to my head or neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive definitive radiation therapy with interim 18FDG-PET/CT imaging to assess response for potential dose de-escalation

7 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute and long-term adverse events

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)
• De-escalated radiation dose
• Standard radiation dose

Trial Overview The study uses advanced imaging (FDG-PET/CT scans) during standard radiation therapy to see if some patients can receive lower doses of radiation safely. It aims to find out if reducing the dose after a positive response affects treatment outcomes.

How Is the Trial Designed?

Group I: Interim PET-CT with dose de-escalation Experimental Treatment 2 Interventions

Participants will receive an interim PET-CT approximately 2 weeks into radiation therapy.

Group II: Interim PET-CT with standard radiation Active Control 2 Interventions

De-escalated radiation dose is already approved in United States, European Union for the following indications:

Approved in United States as De-escalated radiation therapy for:

• HPV-associated oropharyngeal cancer

Approved in European Union as De-escalated radiation therapy for:

• HPV-positive oropharyngeal squamous cell carcinoma

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

Oropharyngeal carcinoma linked to human papillomavirus (HPV) is on the rise, but it has better treatment outcomes compared to traditional head and neck cancers, prompting a focus on treatment de-escalation strategies.

Current strategies for reducing treatment intensity include adjusting radiation doses, using selective nodal irradiation, and evaluating patient responses to induction chemotherapy, all aimed at minimizing side effects while preserving quality of life for younger, healthier patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. Tam, M., Hu, K.[2019]

Oropharyngeal cancers caused by HPV are more sensitive to chemotherapy and radiation, leading to better outcomes compared to HPV-negative cancers, which raises questions about the intensity of current treatment protocols.

Ongoing de-escalation trials suggest that less intensive treatment regimens could maintain efficacy while reducing toxicity for HPV-positive patients, but clinicians are advised to wait for clinical trial results before changing treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. Lahmamssi, C., Guy, JB., Benchekroun, N., et al.[2020]

A systematic review of 10 prospective studies on therapy de-escalation for HPV-associated oropharyngeal cancer (OPC) suggests that reduced-dose chemoradiotherapy, especially when combined with induction chemotherapy, can achieve high 2-year progression-free survival (PFS) rates of 89% and overall survival (OS) rates of 96%.

While de-escalation strategies show promising efficacy, they also present some acute toxicities, with grade 3+ dysphagia and mucositis occurring in 9-39% of patients, indicating a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Patel, RR., Ludmir, EB., Augustyn, A., et al.[2021]

This review aims to compare overall survival rates between standard and reduced-dose radiotherapy in patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), potentially allowing for less toxic treatment options.

The study will include adult patients who have received curative treatment for HPV+ OPSCC, and it will systematically analyze existing literature to determine if lower radiation doses can maintain similar survival outcomes while reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of reduced- versus standard-dose radiotherapy on survival and radiation-associated toxicity in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review protocol. Lee, TJ., Krishnan, G., Ooi, EH., et al.[2022]

HPV-positive oropharyngeal squamous cell carcinoma has a better prognosis and is more sensitive to radiation than HPV-negative cancers, suggesting that lower radiation doses could be effective for treatment.

Recent studies indicate that de-escalated radiation therapy can maintain high cure rates and improve quality of life for selected patients, although challenges remain due to small sample sizes and variability in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies. Chen, AM.[2023]

In a phase II trial involving 80 patients with HPV-associated oropharyngeal cancer, reducing the dose of adjuvant radiotherapy from 60-66 Gy to 30-36 Gy maintained a high locoregional tumor control rate of 96.2% over 2 years.

The study demonstrated low toxicity rates (0% grade 3 or worse toxicity post-treatment) and even slight improvements in swallowing function, indicating that this aggressive dose de-escalation approach can preserve quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. Ma, DJ., Price, KA., Moore, EJ., et al.[2021]

In a study of 759 patients with HPV-positive oropharyngeal squamous cell carcinoma, dose de-escalated radiation therapy (DDRT) did not result in inferior overall survival compared to standard dose radiation therapy (SDRT), with 3-year survival rates of 82.2% for DDRT and 79.3% for SDRT (P = 0.85).

The findings suggest that reducing radiation dose in HPV-positive OPSCC patients may be safe, as there was no significant difference in survival outcomes, indicating that ongoing randomized trials are needed to further explore this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma. Gabani, P., Lin, AJ., Barnes, J., et al.[2020]

De-escalated radiotherapy (RT) is currently used in only 15-20% of patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) in the United States, indicating low adoption despite ongoing trials.

In HPV+ patients, de-escalated RT did not significantly affect overall survival compared to full-dose RT, with 3- and 5-year survival rates being similar, while HPV- patients showed significantly worse survival rates with de-escalated treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer. White, R., Abel, S., Hasan, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10413127/

De-escalated radiation for human papillomavirus virus ... This research showed that HPV-positive head and neck cancer tends to regress early during treatment, reaching a plateau by week 5-6, thus ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.03128

Reduced-Dose Radiation Therapy for HPV-Associated ... Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2788326

Elective Radiotherapy Dose and Field in HPV-Associated ... This cohort study found that the evaluated de-escalation strategy for elective regions showed favorable clinical outcomes and QOL profiles.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1368837524001684

Translational risk-adapted approaches to de-escalated ... These studies have shown that de-escalated radiation for HPV-positive oropharyngeal carcinoma can significantly decrease toxicity while maintaining the ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(19)30021-0/abstract

Radiation therapy dose de-escalation compared to ... After IPTW-adjusted analysis, there was no difference in the 3-yr OS between the two groups (82.2% vs. 79.3%; P = 0.85). In the subset of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12216805/

De‐escalation of radiotherapy in the treatment of human ... Unilateral radiation treatment fields for well‐lateralised oropharyngeal cancers have demonstrated very low rates of locoregional failure in the ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S136883752400407X

Can we safely de-escalate HPV+ oropharyngeal cancers? While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials has failed to demonstrate improved outcomes.

8. jci.org jci.org/articles/view/198351

Genomic adjusted radiation dose stratifies radiotherapy ... Uniform radiation therapy (RT) de-escalation in HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has underperformed in clinical trials ...