Adjuvant Radiation for Throat Cancer

Recruiting at 1 trial location

Overseen By Azeezat Yekinni

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Disqualifiers: Metastatic disease, Prior head/neck cancer, 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)

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 explores a new method for treating throat cancer linked to HPV, a common virus. It examines the effectiveness and manageability of adjusting post-surgery treatments based on ctHPVDNA levels in the blood. Participants are divided into three groups: one receives no further treatment, another receives a lower dose of radiation, and the third receives a higher dose, determined by ctHPVDNA results and other post-surgery factors. Suitable candidates have throat cancer that can be surgically removed and HPV detected in their tumors through blood tests before treatment. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could personalize future cancer treatments.

Do I need to stop my current medications for the trial?

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.

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

Previous studies have tested lower doses of radiation, specifically 30 Gray, for safety. Research has shown that this reduced radiation is safe for patients with HPV-positive throat cancer and is easier to manage, with fewer severe side effects than standard doses.

For the 40 Gray dose, studies suggest it can improve survival rates for patients with certain head and neck cancers. However, evidence indicates that higher doses might lead to more long-term side effects. Despite this, the 40 Gray dose has not shown significant risks of losing control over the cancer's local spread.

Both treatment doses have been studied for safety, but like any radiation therapy, some side effects may occur. These studies help ensure that the treatments remain as safe as possible while still being effective. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the use of ctHPVDNA as a biomarker to guide adjuvant radiation therapy in throat cancer patients. Unlike traditional treatments that often apply a standard radiation dose to all patients, this approach tailors therapy based on the presence or absence of ctHPVDNA, potentially reducing unnecessary radiation exposure. For patients with undetectable ctHPVDNA and minimal lymph node involvement, observation without further treatment could spare them from side effects. Meanwhile, those with positive ctHPVDNA or more extensive disease might receive personalized radiation doses, optimizing treatment efficacy and minimizing harm. This trial could revolutionize how throat cancer is treated by making therapy more personalized and precise.

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

This trial will compare different adjuvant radiation treatments for throat cancer. Research has shown that a lower radiation dose of 30 Gray (Gy) for HPV-positive throat cancer appears promising. Studies have found that 30 Gy can greatly reduce side effects while still effectively controlling the disease. For example, one study reported 100% disease control in certain patients using just 30 Gy.

Meanwhile, the 40 Gray treatment, another arm of this trial, continues to control cancer spread effectively, even with lower radiation doses. Recent trials have demonstrated that 40 Gy provides good disease control without increasing side effects. Both treatments in this trial aim to effectively treat the cancer while minimizing radiation exposure. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Sim, MD

Principal Investigator

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HPV+ squamous cell carcinoma of the oropharynx, who are in good physical condition (ECOG 0-2) and have certain stages of tumor growth. It's open to both smokers and non-smokers with resectable tumors that haven't spread far. Pregnant women, those with recent cancers except some skin/thyroid cases, or previous head/neck cancer/radiation are excluded.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

My tumor is small to medium size and has not spread to my voice box.

My cancer originates in the back of my throat.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I haven't had cancer, except for skin or thyroid cancer, in the last 3 years, or I am cured.

I have HPV-related cancer in my throat.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo transoral surgery and neck dissection

1 week

Adjuvant Treatment

Participants receive adjuvant treatment based on ctHPVDNA levels, including observation or radiation therapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ctHPVDNA

Trial Overview

The study tests if lower doses of adjuvant radiation (30 or 40 Gray), guided by ctHPVDNA levels after surgery and neck dissection, work well for patients with HPV-related throat cancer. This phase II trial aims to see if this approach can effectively treat without standard higher radiation doses.

How Is the Trial Designed?

Group I: Observation Experimental Treatment 1 Intervention

Subjects with undetectable postoperative ctHPVDNA levels and either 4 or fewer nodes will have no further adjuvant treatment.

Group II: Adjuvant Radiation 40 Gray Experimental Treatment 2 Interventions

Subjects with positive postoperative ctHPVDNA will undergo reimaging to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation or 30 Gy of radiation depending on nodal status. If repeat ctHPVDNA level is positive, or subject has no obvious operable disease then subject will undergo 40 Gy of radiation.

Group III: Adjuvant Radiation 30 Gray Experimental Treatment 2 Interventions

Subjects with undetectable postoperative ctHPVDNA levels after surgery, negative margins, and five or more positive nodes; or confirmed extranodal extension (ENE) (greater than 2 mm) will undergo deintensified radiation treatment of 30 gray.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Published Research Related to This Trial

The study proposes a new clinical trial to use circulating tumor DNA (cfHPVDNA) levels to identify patients with HPV-associated oropharyngeal squamous cell carcinoma who may safely undergo de-escalated therapy, potentially reducing long-term treatment toxicity.

Patients with undetectable cfHPVDNA after surgery will be categorized into low-risk or high-risk groups, with low-risk patients possibly receiving observation instead of radiation, while high-risk patients will continue with standard adjuvant therapy, aiming to evaluate disease recurrence and survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Sinai Robotic Surgery Trial in HPV-related oropharyngeal squamous cell carcinoma (SIRS 2.0 trial) - study protocol for a phase II non-randomized non-inferiority trial. Chai, RL., Ferrandino, RM., Barron, C., 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]

A meta-analysis of 13 studies involving 998 patients showed that circulating tumor HPV DNA (ctHPVDNA) detected by ddPCR has high sensitivity (90%) and specificity (94%) for diagnosing HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

The results suggest that ctHPVDNA monitoring could enhance the diagnostic and therapeutic management of cancer patients, providing valuable insights into tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta-analysis. Paolini, F., Campo, F., Iocca, O., et al.[2023]

Weekly dosing of cisplatin significantly reduces the risk of ototoxicity in patients with head and neck squamous cell carcinoma, while maintaining similar progression-free and overall survival rates compared to high-dose cisplatin.

Genetic factors such as the COMT and MATE1 genes can predict ototoxicity risk, with COMT carriers at higher risk and MATE1 A/A carriers showing protection, suggesting that genotyping could help tailor treatment to minimize hearing loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients. Teft, WA., Winquist, E., Nichols, AC., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8778604/

Evaluation of Substantial Reduction in Elective ...

In this cohort study, reduced radiotherapy volume and dose of 30 Gy to the elective regions with concurrent chemotherapy in 276 patients with locally advanced ...

2.

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 ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.24.00395

Selecting Patients With Oropharyngeal Cancer for Lower ...

Forty-two patients (28%) in the current trial had normoxic disease and 100% disease control with only 30 Gy (and two cycles of high-dose cisplatin)!

4.

redjournal.org

redjournal.org/article/S0360-3016(22)00554-5/pdf

A Phase 2 Study of Dose De-escalation for Adjuvant Che

Our study demon- strates that 30 to 36 Gy of adjuvant RT with low-dose docetaxel resulted in low rates of clinically significant long- term ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8168141/

Precision Radiotherapy: Reduction in Radiation for ...

Consistent with this notion, in other HPV-related malignancies, such as anal cancer, 30 Gy and chemotherapy can result in a 95% rate of cure (26) ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18080

ctDNA-guided adjuvant radiation for patients with HPV ...

We designed a phase II study (NCT05387915) to determine if ctHPVDNA can select pathologic intermediate-risk patients for whom adjuvant RT dose could be safely ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02908477

Study Details | NCT02908477 | Evaluation of De-escalated ...

Grade 3+ Adverse Events Rate, To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.

8.

practicalradonc.org

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

Radiation Therapy for HPV-Positive Oropharyngeal ...

Cervical nodal level V can safely be omitted in the treatment of locally advanced oropharyngeal squamous cell carcinoma with definitive IMRT.

9.

ascopost.com

ascopost.com/issues/august-25-2022-supplement-head-neck-almanac/de-escalation-of-radiation-therapy-for-hpv-positive-intermediate-risk-oropharyngeal-cancer/

De-escalation of Radiation Therapy for HPV-Positive ...

De-escalated adjuvant radiotherapy appears to be safe in patients with surgically resectable, human papillomavirus (HPV)--positive oropharyngeal cancers.