ctDNA Testing for Oropharyngeal Cancer

(SAVAL Trial)

Recruiting at 5 trial locations

Overseen By Kelly Kitzmiller, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Disqualifiers: Oral cavity cancer, Distant metastasis, Prior invasive 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

Compensation: Varies

Number of Visits: 1

61 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new blood test called the Circulating Tumor DNA test (ctDNA test) to determine if it can reduce the need for radiation treatment in individuals with HPV-related oropharyngeal cancer. The goal is to limit radiation and its side effects to those who truly need it after surgery. If the ctDNA test is negative post-surgery, patients may skip radiation unless other high-risk factors are present. The study seeks participants diagnosed with specific types of HPV-related oropharyngeal cancer who had a positive ctDNA test before surgery and a negative one after. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer care.

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 the ctDNA test is safe for use in patients with oropharyngeal cancer?

Research has shown that the Circulating Tumor DNA test (ctDNA test) is generally easy for patients to handle. This test monitors cancer by detecting tiny pieces of tumor DNA in the blood. Studies indicate that ctDNA effectively tracks treatment progress and detects cancer recurrence. However, these studies emphasize efficacy over safety issues.

When used for other cancers like lung, colorectal, and breast cancer, ctDNA testing has shown promise, with no major safety problems reported. It's important to note that because this trial is in an early stage, detailed safety information might not be fully available yet. Still, its use in other cancer studies suggests it is safe.

Overall, while specific side effects or problems aren't detailed in the sources, ctDNA testing appears well-tolerated based on its use in different types of cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ctDNA testing approach for oropharyngeal cancer because it offers a personalized way to monitor the disease. Unlike traditional treatments that rely mostly on surgery, radiation, and chemotherapy, ctDNA testing allows doctors to detect cancer DNA in the blood before and after surgery. This method can help identify if a patient is truly cancer-free post-operation, potentially reducing unnecessary treatments. Additionally, it can quickly signal if the cancer returns, enabling faster intervention. This personalized monitoring could lead to more precise treatments and better outcomes for patients.

What evidence suggests that the ctDNA test is effective for reducing radiation in oropharyngeal cancer patients?

Research has shown that tests for circulating tumor DNA (ctDNA) can help manage HPV-related throat cancer. Studies have found that if ctDNA is detected in the blood, the cancer is more likely to return. Conversely, if ctDNA is not found after treatment, patients usually experience better outcomes. In this trial, participants in the experimental observation arm will undergo monitoring with ctDNA tests to determine the necessity of additional treatments, such as radiation. This approach aims to personalize treatment by administering radiation only to those who need it, potentially reducing unnecessary side effects for others. ^{2 3 6 7 8}

Who Is on the Research Team?

Jason Molitoris, MD

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Are You a Good Fit for This Trial?

This trial is for adults with HPV-related oropharyngeal cancer, without distant metastasis, who haven't had prior invasive malignancies (except some skin cancers and low-risk prostate cancer) in the last 3 years. They should be candidates for a specific surgical technique (TORS), have positive ctDNA levels before surgery, and agree to use effective contraception if applicable.

Inclusion Criteria

My cancer is in an early or middle stage and hasn't spread far.

My tests show cancer DNA in my blood or biopsy before surgery.

A team of doctors agrees I can have robotic surgery for my tumor.

Exclusion Criteria

I have had surgery for cancer in my head or neck area, not including minor skin cancer removals.

I have not had chemotherapy for my current cancer, but may have had it for another cancer.

My cancer has spread to distant parts of my body.

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 (TORS) and have ctDNA drawn within 2-14 days post-operatively

2-3 weeks

1 visit (in-person)

Observation

Intermediate risk group is observed without radiation; monitored for toxicity, Quality of Life (QoL), and outcomes evaluation

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of recurrence and quality of life

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Adjuvant Treatment per Standard of Care
• Circulating Tumor DNA test (ctDNA test)
• Experimental Observation
• Observation per Standard of Care

Trial Overview The study aims to see if using a blood test called Circulating Tumor DNA test (ctDNA test) can reduce the need for radiation therapy after surgery in patients with HPV-related oropharyngeal cancer. The idea is that only those who really need radiation due to high risk will receive it based on their ctDNA results post-surgery.

How Is the Trial Designed?

Group I: Intermediate Risk Experimental Observation Experimental Treatment 4 Interventions

Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy).

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study of 66 patients with HPV16-positive oropharyngeal squamous cell carcinoma, 71% had detectable HPV circulating tumoral DNA (ctDNA) at diagnosis, indicating its potential as a predictive biomarker for disease severity.

The amount of HPV16 ctDNA was significantly linked to cancer staging and was associated with treatment outcomes, suggesting that monitoring ctDNA could help tailor treatment strategies and assess response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV circulating tumoral DNA quantification by droplet-based digital PCR: A promising predictive and prognostic biomarker for HPV-associated oropharyngeal cancers. Veyer, D., Wack, M., Mandavit, M., et al.[2021]

This exploratory study demonstrated that low levels of circulating tumor DNA (ctDNA) containing TP53 mutations can be detected in the plasma of head and neck cancer patients using Droplet Digital PCR (ddPCR), indicating its potential as a biomarker for monitoring tumor burden.

All six patients with advanced head and neck squamous cell carcinoma tested positive for specific TP53 mutations in their plasma, suggesting that ctDNA analysis could be a feasible method for early detection of disease relapse during posttreatment surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. van Ginkel, JH., Huibers, MMH., van Es, RJJ., et al.[2019]

HPV-related oropharyngeal squamous cell carcinoma (OPSCC) generally has better treatment outcomes compared to non-virally mediated cancers, prompting research into strategies that reduce treatment toxicity while maintaining survival rates.

Circulating tumor (ct) DNA is a promising biomarker for monitoring treatment response and disease recurrence in head and neck cancers, particularly in HPV-related OPSCC, suggesting potential for its integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of circulating tumor DNA as a biomarker in HPV related oropharyngeal squamous cell carcinoma. Haring, CT., Dermody, SM., Yalamanchi, P., et al.[2022]

Circulating tumor DNA (ctDNA) levels in cancer patients can provide important prognostic information, as higher levels of ctDNA at diagnosis are associated with greater tumor burden and more aggressive disease.

Persistent ctDNA levels after treatment may indicate a higher risk of tumor relapse, potentially allowing for earlier intervention strategies like dose-escalation of radiotherapy or additional chemotherapy and immunotherapy in at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using Liquid Biopsy to Predict Relapse After Radiotherapy in Squamous Cell Head-Neck and Esophageal Cancer. Koukourakis, IM., Xanthopoulou, E., Koukourakis, MI.[2023]

Circulating tumor DNA (ctDNA) is a promising biomarker for diagnosing and monitoring human papillomavirus-related oropharyngeal squamous cell carcinoma, potentially improving patient management.

Changes in ctDNA levels during and after treatment may indicate disease response, which could inform decisions on whether to intensify or reduce treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Role of Human Papillomavirus Circulating Tumor DNA in Oropharynx Cancer. Regan, SN., Mierzwa, ML.[2023]

Circulating tumor DNA (ctDNA) is a promising biomarker in oropharyngeal squamous cell carcinoma, particularly for patients with human papillomavirus (HPV)-related cancers, as it may help in assessing prognosis and monitoring treatment response.

Current research highlights the importance of understanding ctDNA dynamics, especially in clinical trials aimed at treatment de-escalation, indicating its potential role in detecting minimal residual disease and guiding future therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions. Heft Neal, ME., Walline, HM., Haring, CT.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1368837525000910

Review Circulating tumor DNA in human papillomavirus ... Circulating tumor DNA (ctDNA) has emerged as a promising tool in the treatment of HPV-associated oropharyngeal squamous cell cancer (OPSCC).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11580464/

The effect of circulating tumor DNA on the prognosis ... The meta-analysis demonstrated that the positive ctDNA/methylation detection was associated with worse OS (HR = 2.00, 95% CI 1.35–2.96) and ...

3. nature.com nature.com/articles/s41698-025-00876-y

Circulating tumor DNA to monitor treatment response in ... In this review, we provide a comprehensive, up-to-date summary of ctDNA in monitoring treatment response with a focus on lung, colorectal, and breast cancers.

4. ajnr.org ajnr.org/content/45/8/1135

Preliminary Results from Retrospective Correlation of ... The study showed a strong positive correlation between the imaging findings and the ct-DNA level in recurrent HPV-positive oropharyngeal ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03940-6/fulltext

Tumor-agnostic plasma assay for circulating tumor DNA ... For pre-treatment ctDNA-positive patients, the 2-year PFS rate was 23.5% (95% CI 10% to 55%) and 86.6% (95% CI 73.4% to 100%) in MRD-positive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12032849/

A Review of Circulating Tumor DNA (ctDNA) and the Liquid ... This article aims to review ctDNA and liquid biopsy in the diagnosis, early detection, and monitoring of treatment response in cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7106982/

Plasma Circulating Tumor HPV DNA for the Surveillance of ... A recent prospective biomarker study investigated oral HPV DNA testing during post-treatment surveillance and reported NPV 86% and PPV 43% for recurrence ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04900623

Study Details | NCT04900623 | Risk-adapted Therapy in ... This testing has shown promise in early detection of cancer recurrence in several solid tumor types (including colorectal, urothelial, and breast cancer).