Reduced-Dose Radiation Therapy for Oropharyngeal Cancer

Not currently recruiting at 2 trial locations

Overseen By James Bates, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Investigational agents

Disqualifiers: Recent malignancy, Chemotherapy, Cardiovascular, 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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a lower dose of radiation therapy after surgery can benefit people with HPV-positive oropharyngeal cancer. This type of cancer generally has a better prognosis than others, but standard treatment often leads to long-term side effects, such as difficulty swallowing. The study seeks to determine if reducing the radiation dose can enhance swallowing and overall quality of life. It suits individuals diagnosed with HPV-related oropharyngeal cancer who have completed specific robotic surgery and have a limited smoking history. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to potentially improving future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational drugs or have had recent chemotherapy or radiotherapy, you may not be eligible to participate.

Is there any evidence suggesting that reduced dose radiation therapy is likely to be safe for humans?

Studies have shown that lowering the radiation dose for patients with HPV-positive oropharyngeal cancer can be safe. Research has tested reduced radiation for these patients and found it can lessen side effects without compromising effectiveness. For instance, one study showed very high survival rates, about 97%, even with the reduced dose. Lowering the radiation dose may improve quality of life by reducing long-term side effects like trouble swallowing. This suggests that patients with this type of cancer can tolerate reduced-dose radiation therapy well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for oropharyngeal cancer?

Researchers are excited about the reduced-dose radiation therapy for oropharyngeal cancer because it offers a potentially less intense treatment option with the same effectiveness. Unlike standard radiation treatments, which can be lengthy and intense, this approach reduces the radiation exposure for patients who test ctHPVDNA negative after surgery, potentially leading to fewer side effects and improved quality of life. By tailoring the radiation dose to the patient's specific needs, this method aims to maintain treatment effectiveness while minimizing the harmful impacts often associated with traditional radiation therapy.

What evidence suggests that reduced dose radiation therapy might be an effective treatment for HPV-positive oropharyngeal cancer?

Research has shown that lowering the radiation dose for patients with HPV-positive throat cancer can greatly reduce treatment side effects. In this trial, patients who are ctHPVDNA negative after surgery will undergo reduced-dose radiation therapy. Studies have found that patients who received less radiation experienced fewer negative effects and enjoyed a better quality of life. A review of multiple studies also found that this method can still effectively control cancer while causing less harm to healthy tissue. Additionally, clinical trials have demonstrated that in certain cases, using lower radiation doses is both safe and effective for treating this type of cancer. Overall, the evidence suggests that reduced-dose radiation can be a promising option for those with HPV-related throat cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

James E Bates, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

Adults with HPV-positive oropharyngeal cancer who've had surgery and limited smoking history can join this trial. They must have a life expectancy over 12 weeks, be in good enough health to perform daily activities, and agree to use contraception. Those with extensive cancer spread, recent other cancers, or severe illnesses are excluded.

Inclusion Criteria

My cancer has one of the following: close margin, perineural invasion, lymphovascular invasion, 2-4 positive lymph nodes without ENE, or a single lymph node larger than 3 cm without ENE.

Life expectancy > 12 weeks as determined by the Investigator

Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

Exclusion Criteria

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

Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs

I have not had cancer, except for non-dangerous skin cancer, in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo transoral robotic surgery to remove the tumor

1 week

1 visit (in-person)

Radiation Therapy

Participants receive reduced dose radiation therapy for 3 weeks if ctHPVDNA negative, or standard of care radiation therapy if ctHPVDNA positive

3 weeks

15 treatments (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 3, 6, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview The trial is testing if lower doses of radiation therapy after robotic surgery improve swallowing and quality of life for patients with HPV-positive throat cancer compared to the standard higher doses usually given after such surgeries.

How Is the Trial Designed?

Group I: Treatment (reduced dose radiation therapy) Experimental Treatment 1 Intervention

Patients who are ctHPVDNA negative after surgery undergo reduced dose radiation therapy for 3 weeks (15 treatments). Patients who are ctHPVDNA positive after surgery undergo standard of care radiation therapy.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intensity-modulated radiation therapy (IMRT) significantly reduced the incidence of late xerostomia (dry mouth) in patients with oropharyngeal cancer compared to conventional radiation therapy (CRT), indicating a safety advantage for IMRT.

The study, which followed 430 patients over a median of 3.9 years, found that IMRT did not negatively affect tumor control or disease-free survival rates, demonstrating its efficacy in treating oropharyngeal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Chao, KS., Majhail, N., Huang, CJ., et al.[2022]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

Modern radiation therapy, particularly intensity-modulated radiation therapy (IMRT), significantly reduces xerostomia (dry mouth) and improves the quality of life for patients with oropharyngeal cancer.

Intensity-modulated proton therapy may offer even greater benefits by minimizing radiation-related toxicities, which is crucial for patients with HPV-positive oropharyngeal carcinoma who are likely to have long-term survival after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in radiation oncology for the management of oropharyngeal tumors. Gunn, GB., Frank, SJ.[2018]

Intensity Modulated Radiation Therapy (IMRT) combined with Image Guided Radiation Therapy (IGRT) enhances treatment for head and neck cancer by improving tumor coverage while minimizing damage to normal tissues, leading to similar tumor control rates with less toxicity compared to conventional methods.

In the context of systemic therapy, platinum-based radiochemotherapy remains the standard treatment, and early evidence suggests that adding Cetuximab to cisplatin-based therapy does not provide additional benefits in primary treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. Pütz, M., Wenz, F.[2021]

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 radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

In a study of 148 oropharynx cancer patients treated with either IMRT alone or a combination of IMRT and IMPT, the combination therapy showed significantly lower rates of severe acute toxicities, such as mucositis and pain, indicating a safer treatment option.

Despite similar overall survival and progression-free survival rates between the two groups, the IMRT/IMPT combination resulted in fewer patients experiencing grade ≥ 3 mucositis and pain, suggesting improved patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients. Yoon, HG., Ahn, YC., Oh, D., et al.[2021]

Patients with oropharyngeal carcinoma (OPC) treated with intensity-modulated proton therapy (IMPT) experienced significantly lower rates of acute toxic effects compared to those treated with intensity-modulated radiation therapy (IMRT), including less oral pain, xerostomia, and dysphagia.

Despite the reduced toxicity, both IMPT and IMRT showed similar oncologic outcomes, with 3-year overall survival rates of 97% for IMPT and 91% for IMRT, indicating that IMPT is a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. Youssef, I., Yoon, J., Mohamed, N., et al.[2023]

Intensity-modulated radiation therapy (IMRT) can significantly reduce the amount of mucosal tissue exposed to high radiation doses in patients with early oropharyngeal cancer, especially when a dose objective is set for the mucosa.

In a study involving 5 patients, IMRT with a mucosal dose objective resulted in up to a 30% reduction in mucosal exposure to high doses compared to standard three-field technique (3FT) radiotherapy, indicating that IMRT may offer a safer treatment option with less risk of damaging healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a "mucosa-sparing" benefit of IMRT for head-and-neck cancer? Sanguineti, G., Endres, EJ., Gunn, BG., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9843369/

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

Reduced-Dose Radiation Therapy for HPV-Associated ... Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36660712/

Reduced-dose radiation in human papillomavirus ... Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis. Ann Transl Med. ...

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

Elective Radiotherapy Dose and Field in HPV-Associated ... Several clinical trials have shown that in patients with select HPV-positive OPC, radiation dose to gross disease can be safely reduced, ...

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

Radiation Therapy for HPV-Positive Oropharyngeal ... The goal of such studies is to maintain cure rates and minimize the acute and long-term effects of treatment on multiple functions ranging from ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078254/

Reduced-Dose Radiation Therapy for HPV-Associated ... Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07178301

Evaluating a Decreased Dose of Radiation Therapy to the ... Reducing the dose of radiation therapy to the lymph nodes in the neck that aren't directly involved in the cancer may improve patient quality of ...

8. nrgoncology.org nrgoncology.org/Home/News/Post/reduced-dose-radiation-with-cisplatin-improves-outcomes-for-hpv-associated-oropharyngeal-carcinoma-patients-on-nrg-oncology-study-justifies-phase-iii-trial

Reduced-Dose Radiation with Cisplatin Improves Outcomes f 2-year overall survival rates were 96.7% and 97.3% for the IMRT+C and the IMRT alone arms, respectively. While more grade 3-4 acute toxicities ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850018303163

Reducing the Radiation Therapy Dose Prescription for ... We have altered our radiation guidelines to allow substantial dose reduction to elective treatment regions and to omit radiation completely in other regions.