De-intensified Radiotherapy for Oropharyngeal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Steroids, Immunosuppressive drugs

Disqualifiers: Metastatic disease, Oral cavity cancers, Prior malignancy, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using radiation therapy to treat HPV-related oropharyngeal cancer, which affects areas like the tonsils and base of the tongue. Researchers aim to determine if a blood test can guide a lower dose of radiation (adaptive de-intensified radiotherapy) to be as effective as the usual higher dose. Participants will be divided into two groups: one receiving reduced radiation if their blood shows a drop in tumor DNA, and the other receiving the standard treatment if it does not. The trial seeks individuals with HPV-related throat cancer who have a smoking history of 10 pack years or less and have measurable disease confirmed by medical imaging. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on steroids or immunosuppressive medications, you may need to stop them 14 days before joining the trial.

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

Research shows that a new type of radiation treatment, called adaptive de-intensified radiotherapy, is being tested for HPV-positive oropharyngeal cancer. This treatment uses lower doses of radiation to reduce side effects while still effectively treating the cancer. Studies suggest that this approach may lessen side effects like difficulty swallowing, which is common in head and neck cancer patients.

Patients who tried this treatment generally experienced fewer severe side effects compared to those who received traditional radiation therapy. Researchers hope this method could offer a safer option with fewer negative reactions. However, this treatment is still under study, and further research will clarify its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the adaptive de-intensified radiotherapy approach for oropharyngeal cancer because it offers a personalized treatment strategy that aims to reduce side effects while maintaining effectiveness. Unlike the standard of care, which typically involves a fixed radiotherapy schedule for all patients, this method adapts the treatment intensity based on the patient’s response, specifically their tumor's molecular characteristics. By tailoring the therapy according to the reduction of circulating tumor DNA, this approach could potentially decrease the treatment burden for patients who respond well, without compromising the overall outcome.

What evidence suggests that adaptive de-intensified radiotherapy might be an effective treatment for oropharyngeal cancer?

This trial will compare two approaches to de-intensified radiotherapy for HPV-related throat cancer. Research has shown that a flexible approach to reducing radiotherapy can be promising. This method, called adaptive radiotherapy, adjusts treatment based on changes in tumor size and may help reduce side effects like dry mouth. One study found that changing the radiation dose improved survival rates without harming nearby healthy tissues. Early findings also suggest that checking HPV levels in the blood can help safely lower radiation doses. This approach aims to maintain treatment effectiveness while reducing overall radiation exposure. ^{1 3 6 7 8}

Who Is on the Research Team?

Sujith Baliga, M.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with HPV-associated oropharyngeal cancer. Participants must have detectable human papillomavirus in their blood and be suitable for chemotherapy combined with radiation therapy. Specific details on inclusion and exclusion criteria are not provided.

Inclusion Criteria

Absolute neutrophil count: ≥ 1500/mcL

Platelets: >= 100,000/mcL

For women of childbearing potential, negative serum or urine pregnancy test within 14 days of registration

Exclusion Criteria

I have received chemotherapy or immunotherapy before.

Patients who are pregnant, nursing, or expected to conceive or father children

Patients who are allergic to cisplatin, carboplatin, or paclitaxel

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Treatment

Participants undergo external beam radiotherapy and receive chemotherapy for 4 weeks. Blood samples are collected for circulating tumor DNA testing.

4 weeks

5 visits per week (in-person)

Adaptive Treatment

Based on circulating tumor DNA results, participants continue with adjusted radiotherapy and chemotherapy for 5 to 7 weeks.

5-7 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PET/CT scans and adverse event evaluations.

24 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Adaptive De-intensified Radiotherapy

Trial Overview The study tests if lower dose radiation guided by circulating tumor DNA levels can effectively treat HPV-related oropharyngeal cancer, compared to standard higher dose radiation with chemotherapy. It involves questionnaires, PET/CT scans, biospecimen collection, and drugs like Carboplatin, Cisplatin, Paclitaxel.

How Is the Trial Designed?

Group I: Arm I (reduced > 95% of TTMV, external beam radiotherapy) Experimental Treatment 8 Interventions

Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4. Patients with reduced \> 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.

Group II: Arm II (not reduced > 95% of TTMV, external beam radiotherapy) Active Control 8 Interventions

Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4. Patients without reduced \> 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.

Adaptive De-intensified Radiotherapy is already approved in United States, European Union for the following indications:

Approved in United States as Adaptive De-intensified Radiotherapy for:

• HPV-associated oropharyngeal cancer

Approved in European Union as De-intensified Radiotherapy for:

• HPV-positive oropharyngeal squamous cell carcinoma

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Published Research Related to This Trial

In a phase 2 clinical trial involving 60 patients with HPV-associated oropharyngeal squamous cell carcinoma, a novel deintensified radiation therapy approach resulted in a remarkable 2-year local control rate of 98.3%, indicating high efficacy in preventing cancer recurrence after surgery.

The treatment was found to be safe, with only 3.3% of patients experiencing late soft tissue necrosis that resolved quickly, and no patients required feeding tubes during or after treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx. Swisher-McClure, S., Lukens, JN., Aggarwal, C., et al.[2020]

In a study involving 20 patients with poor prognosis oropharyngeal squamous cell carcinoma, researchers demonstrated that it is feasible to escalate radiation doses to the gross tumor volume (GTV) without significantly increasing doses to surrounding healthy tissues or planning target volumes (PTVs).

The study found that while doses to the GTV could be increased by up to 26.2%, the increase in doses to organs at risk (OAR) was not clinically significant, indicating that this adaptive radiation therapy approach could be safely implemented in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive dose escalated radiotherapy in oropharyngeal cancers: a treatment planning feasibility study. Grocutt, L., Paterson, C., Valentine, RM.[2022]

The phase III GORTEC-REACH trial found that combining immune checkpoint inhibitors with radiotherapy for locally advanced head and neck cancer was less effective than traditional platinum-based chemoradiotherapy, although it may still be better than using EGFR inhibition alone.

Initial phase II trials suggest that dose de-escalation of radiotherapy is feasible for HPV-positive oropharyngeal cancer, but this approach should only be conducted within clinical trials to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer]. Hecht, M., von der Grün, J., Semrau, S., et al.[2022]

In a study of 857 patients with oropharyngeal cancer who had low smoking exposure, the 2-year progression-free survival (PFS) rate was an impressive 91%, indicating favorable outcomes for this low-risk group.

Patients treated with radiation alone showed similar high PFS rates (90% at 2 years and 85% at 5 years) compared to those receiving systemic therapy, suggesting that de-intensifying treatment may not compromise survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus-associated oropharyngeal cancer. Garden, AS., Fuller, CD., Rosenthal, DI., et al.[2018]

Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) have a significantly better prognosis and are more sensitive to radiation compared to HPV-negative cases, allowing for treatment de-escalation with lower doses of radiation and chemotherapy.

Prospective 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-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration. Chen, AM.[2023]

HPV-associated oropharyngeal squamous cell carcinomas respond well to radiation and chemotherapy, leading to a generally favorable prognosis, which supports the exploration of treatment de-intensification strategies.

Transoral Robotic Surgery combined with reduced adjuvant therapy shows promise in minimizing treatment toxicity while maintaining effectiveness, and personalized approaches using tumor biology and imaging markers are helping to further tailor and reduce the intensity of radiotherapy and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV-associated oropharyngeal cancer de-escalation strategies and trials: Past failures and future promise. Zakeri, K., Dunn, L., Lee, N.[2022]

Patients with HPV-positive oropharyngeal cancer who underwent risk- and response-adapted de-escalated radiation therapy (RT) and chemoradiation (CRT) showed significantly better functional outcomes, including improved swallowing function and higher body mass index (BMI), compared to those receiving standard high-dose treatment.

The study found that lower treatment intensity (RT50/CRT45) was associated with less PEG-tube dependency and reduced narcotic use, highlighting the benefits of de-escalation in treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. Foster, CC., Seiwert, TY., MacCracken, E., et al.[2021]

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 clinical trial involving 114 patients with HPV-associated oropharyngeal cancer, a de-intensified treatment regimen of 60 Gy radiotherapy and low-dose cisplatin resulted in excellent 2-year outcomes: 95% local-regional control and 86% progression-free survival.

The study found that this treatment approach minimized the need for chemotherapy and surgery, with no severe late adverse events reported, indicating a safer and effective option for patients with minimal smoking history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Chera, BS., Amdur, RJ., Green, R., et al.[2021]

In a study of 215 patients with oropharyngeal cancer, dose-escalated radiotherapy (over 72 Gy) showed a 5-year overall survival rate of 77.8%, which was not significantly different from the 73.7% survival rate in a matched group receiving standard dose radiotherapy (68 Gy).

However, patients receiving dose-escalated treatment experienced higher rates of severe side effects, including grade ≥3 osteoradionecrosis (8.8% vs. 1.9%) and grade ≥3 dysphagia (18.1% vs. 9.8%), indicating a need for careful patient selection for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Escalation of Oropharyngeal Cancer: Long-Time Follow-Up and Side Effects. Embring, A., Onjukka, E., Mercke, C., et al.[2023]

HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct type of cancer that may benefit from personalized treatment strategies, including less invasive and less toxic therapies.

Current research is focused on de-escalation treatment strategies that aim to reduce the toxicity of standard treatments while maintaining effective disease control, but more conclusive results from ongoing trials are needed to determine the best approaches and which patients will benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma. De Virgilio, A., Costantino, A., Mercante, G., et al.[2021]

In a pilot study of 22 patients with oropharyngeal squamous cell carcinoma, adaptive radiotherapy (ART) demonstrated 100% local disease control and 95% regional control at a median follow-up of 31 months, indicating its efficacy in managing advanced head-and-neck cancer.

The study found that acute toxicity levels were similar to those seen with conventional intensity-modulated radiotherapy (IMRT), suggesting that ART is a safe treatment option with potential benefits in functional recovery and disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a prospective trial. Schwartz, DL., Garden, AS., Thomas, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06323460

Study Details | NCT06323460 | Adaptive De-intensified ... This phase II trial studies how well using circulating tumor deoxyribonucleic acid (DNA) to guide lower dose radiation therapy works in treating patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4271827/

Adaptive Radiotherapy for Head and Neck Cancer To present pilot toxicity and survival outcomes for a prospective trial investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell carcinoma.

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2805682

Weekly Adaptive Radiotherapy vs Standard Intensity ... We hypothesized that ART might decrease the rate of xerostomia in locally advanced oropharyngeal carcinoma compared with standard CT scan–based ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8817487/

Adaptive dose escalated radiotherapy in oropharyngeal cancers The aim of this study is to assess the feasibility of adaptive and dose-escalated RT to the gross tumour volume without increasing surrounding planning target ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405631625000016

Adaptive radiotherapy in locally advanced head and neck ... In the ARTIX trial, a phase 3 randomized trial of 132 oropharyngeal cancer patients, ART did not significantly improve patient-reported outcomes, or rates of ...

6. withpower.com withpower.com/trial/phase-2-carcinoma-3-2024-4c73c

De-intensified Radiotherapy for Oropharyngeal Cancer Adaptive De-intensified Radiotherapy is unique because it uses lower doses of radiation specifically for HPV-positive oropharyngeal cancer, which is more ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8560706/

Patient-Reported Outcomes-Guided Adaptive Radiation ... Dysphagia-focused ART may provide the greatest toxicity benefit to head and neck cancer patients, and represent a potential new direction for ART.

8. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-022-01991-x

Adaptive dose escalated radiotherapy in oropharyngeal cancers The aim of this study is to assess the feasibility of adaptive and dose-escalated RT to the gross tumour volume without increasing surrounding planning target ...