De-intensified Radiotherapy for Oropharyngeal Cancer

Overseen by Sujith Baliga, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well using circulating tumor deoxyribonucleic acid (DNA) to guide lower dose radiation therapy works in treating patients with human papillomavirus infection (HPV)-associated oropharyngeal cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Recently, a blood test has been developed to detect the human papillomavirus in the blood and determine how many viral particles are present. Researchers want to compare any good and bad effects of using the lower dose radiation therapy with chemotherapy compared to the usual standard of care dose chemotherapy in patients who clear the human papillomavirus particles from their blood.

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.

What data supports the effectiveness of the treatment De-intensified Radiotherapy for Oropharyngeal Cancer?

Research shows that de-intensified radiotherapy for HPV-associated oropharyngeal cancer can lead to similar survival outcomes as current therapies but with less toxicity, especially for patients with a lower risk of disease recurrence. Additionally, adaptive radiotherapy has shown promising initial outcomes in terms of reducing side effects while maintaining effectiveness. ^{1 2 3 4 5}

Is de-intensified radiotherapy safe for humans?

Research on de-intensified radiotherapy for oropharyngeal cancer, particularly in patients with HPV-associated cancer, suggests it is generally safe with favorable outcomes. However, some studies indicate that higher doses can lead to side effects like osteoradionecrosis (bone damage) and dysphagia (difficulty swallowing), so careful monitoring is important. ^{2 3 6 7 8}

How is Adaptive De-intensified Radiotherapy different from other treatments 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 sensitive to radiation. This approach aims to maintain high cure rates while reducing side effects, unlike traditional treatments that use higher radiation doses. ^{2 9 10 11 12}

Research Team

Sujith Baliga, M.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Adaptive De-intensified Radiotherapy (Radiation)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

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 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 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]

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 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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer]. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Adaptive dose escalated radiotherapy in oropharyngeal cancers: a treatment planning feasibility study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus-associated oropharyngeal cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy for head-and-neck cancer: initial clinical outcomes from a prospective trial. [2022]

6. United States 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Dose Escalation of Oropharyngeal Cancer: Long-Time Follow-Up and Side Effects. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

De-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

HPV-associated oropharyngeal cancer de-escalation strategies and trials: Past failures and future promise. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma. [2021]