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

Trial Summary

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 data supports the effectiveness of the treatment for oropharyngeal cancer?

Research shows that circulating tumor DNA (ctDNA) can be a useful biomarker for monitoring treatment response and predicting outcomes in HPV-related oropharyngeal cancer. Studies have found that ctDNA levels correlate with tumor burden and can help identify patients who might benefit from adjusted treatment strategies. ^{1 2 3 4 5}

Is ctDNA testing for oropharyngeal cancer safe for humans?

The research articles focus on the potential of ctDNA testing as a biomarker for monitoring cancer but do not provide specific safety data for humans. However, ctDNA testing is a noninvasive blood test, which generally suggests a low risk of harm. ^{1 2 3 4 5}

How does ctDNA testing differ from other treatments for oropharyngeal cancer?

ctDNA testing is unique because it uses a blood test to detect and monitor tumor DNA, helping to predict treatment response and detect cancer recurrence earlier than traditional methods. This approach is noninvasive and can guide personalized treatment strategies, potentially allowing for treatment adjustments based on individual patient needs. ^{1 2 3 4 6}

What is the purpose of this trial?

Patients with human papillomavirus (HPV)-related oropharyngeal cancer generally have favorable outcomes and how well they do depends on the specific details about the patient and their cancer. How well they do isn't as related to the kinds of treatment they get. However, there are significant side effects for the various types of treatments they may get. Because these patients generally have favorable outcomes no matter the kind of treatment, reducing side effects should be a priority when choosing their treatment. The goal of this clinical research study is to evaluate whether a new blood test called a Circulating Tumor DNA test (ctDNA test) can decrease the number of people that require radiation after surgery. This blood test is often elevated in people when they are diagnosed with head and neck cancer. There are studies that show that cancer most often returns when this blood test is positive after treatment. This study will test patients' blood before and after surgery. In cases where the test is negative after surgery, people on the study will not receive radiation unless they are considered high risk based on surgery findings. The hope is that radiation and its potential side effects can be limited to only people that need the treatment.

Research Team

Jason Molitoris, MD

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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]

References

1. United States 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The future of circulating tumor DNA as a biomarker in HPV related oropharyngeal squamous cell carcinoma. [2022]

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

Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Using Liquid Biopsy to Predict Relapse After Radiotherapy in Squamous Cell Head-Neck and Esophageal Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. [2019]

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

The Current Role of Human Papillomavirus Circulating Tumor DNA in Oropharynx Cancer. [2023]