ctDNA Testing for Oropharyngeal Cancer

Recruiting at 8 trial locations

Overseen By Acharf Shamseddine, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Metastatic disease, Non-HPV16, Prior radiation, 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: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a blood test detecting HPV ctDNA (tiny pieces of DNA from the virus that could indicate cancer) can predict the risk of oropharyngeal cancer returning after surgery. The study aims to determine if this test can guide decisions on safely delaying radiation therapy or shortening the usual combined treatment of chemoradiation (a combination of chemotherapy and radiation therapy). Individuals who recently underwent surgery for HPV-related oropharyngeal cancer and show no visible cancer on scans might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that chemoradiation can cause some side effects. In past studies, participants experienced issues like low white blood cell counts, constipation, and ringing in the ears. However, these side effects are often manageable. Chemoradiation is a common treatment, suggesting it is generally safe despite these possible side effects.

Regarding the HPV ctDNA test, research indicates it is a promising method for tracking HPV-related cancers. This test uses a blood sample to detect cancer markers and is considered accurate, effectively identifying the target with few false alarms. No significant safety concerns have been reported with this test.

Overall, both treatments have distinct safety profiles. Chemoradiation may cause some side effects, but it remains a well-established treatment. The HPV ctDNA test is newer and appears safe based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores using HPV ctDNA assays to tailor treatment for oropharyngeal cancer, potentially setting a new standard. Unlike current treatments that rely primarily on fixed regimens of chemoradiation and surgery, this approach personalizes therapy based on the presence of HPV ctDNA, allowing for potentially less aggressive treatment when appropriate. By utilizing ctDNA to monitor cancer status, the trial aims to reduce unnecessary exposure to high doses of radiation and chemotherapy, minimizing side effects while maintaining effectiveness. This innovative approach could lead to more targeted, efficient, and patient-friendly cancer care.

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

Research has shown that combining chemotherapy and radiation, known as chemoradiation, leads to better outcomes for early-stage HPV-positive throat cancers. This method is the most effective treatment for many patients, helping them live longer without the cancer worsening. In this trial, participants in Arm B will receive a de-escalated version of this treatment. Meanwhile, a new blood test called the HPV ctDNA assay is becoming a useful tool for tracking these cancers. Participants in Arm A will undergo active surveillance using this assay. Studies indicate that checking for HPV DNA in the blood can help predict cancer progression and may even detect the risk of recurrence. Both treatments are supported by research and offer potential benefits for managing HPV-positive throat cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Acharf Shamseddine, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with HPV-16 related oropharyngeal cancer who've had surgery to remove the tumor and show no signs of cancer in post-op imaging. They must have certain blood markers, good organ function, and be able to consent. People with metastatic disease, non-HPV16 cancers, prior chemo for this cancer, severe health issues like recent heart failure or infections can't join.

Inclusion Criteria

My post-surgery HPV cancer tests were negative twice.

My cancer has spread beyond its original location or has cells at the surgery margin.

Signed informed consent form by the participant or their legally authorized representative (LAR).

Exclusion Criteria

Severe, active co-morbidity defined as follows: - Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months - Transmural myocardial infarction within the last 6 months - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of registration - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects - Lack of ability to understand and willingness to sign a written informed consent and complete questionnaires.

My cancer has spread to other parts of my body.

I have cancer in areas other than the oropharynx.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Active Surveillance

Monitoring of HPV ctDNA levels to determine the need for radiation therapy

Up to 4 weeks

Regular monitoring visits

Treatment (Arm A)

Delayed standard of care adjuvant radiation based on HPV ctDNA levels

50-60 Gy administered in 1.8-2 Gy fractions

Multiple visits for radiation therapy

Treatment (Arm B)

De-escalated treatment with adjuvant radiation and concurrent chemotherapy

3 weeks

Multiple visits for radiation and chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Chemoradiation
• HPV ctDNA Assay
• Intensity-Modulated Radiation Therapy

Trial Overview

The study tests if monitoring cell-free tumor DNA (ctDNA) levels can guide treatment timing after surgery. Arm A explores delaying radiation therapy until ctDNA is detectable again. Arm B checks if patients normally needing longer chemoradiation could receive a shorter 3-week course based on their ctDNA levels.

How Is the Trial Designed?

Group I: Screening, active surveillance, and treatment (Arm A) Experimental Treatment 6 Interventions

Participants who meet criteria for the treatment phase (a post-operative HPV ctDNA which rose from initial undetectable to meet HPV16 ctDNA criteria and have no clinical or radiographic evidence of gross disease) will undergo delayed standard of care adjuvant radiation (50-60 Gy administered in 1.8-2 Gy fractions) based on the patient's initial pathology. Treatment will be initiated within 4 weeks of a NavDx result. Subjects will undergo FDG PET/CT simulation and standard radiation treatment planning and this FDG PET/CT will also be utilized to rule out distant metastases. Diagnostic FDG PET/CT fusion is also allowed for treatment planning and to rule out distant metastases. Non-therapeutic assessments will be completed.

Group II: Screening and deescalated treatment (Arm B) Experimental Treatment 6 Interventions

Participants who meet criteria for the de-escalated treatment phase (Arm B) will undergo adjuvant radiation (30 Gy administered in 2 Gy fractions) with concurrent chemotherapy. They will undergo FDG PET/CT simulation and standard radiation treatment planning and this FDG PET/CT will also be utilized to rule out distant metastases. Diagnostic FDG PET/CT fusion is also allowed for treatment planning and to rule out distant metastases. Non-therapeutic assessments will be completed and the Study calendar.

Chemoradiation is already approved in China for the following indications:

Approved in China as Baizean for:

• Classical Hodgkin’s lymphoma (cHL)
• Locally advanced or metastatic urothelial carcinoma (UC)
• Locally advanced or metastatic non-small cell lung cancer (NSCLC)
• Advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
• Locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Recurrent or metastatic nasopharyngeal cancer (NPC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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]

In a study of 34 patients with stage III oropharyngeal squamous cell carcinoma, low levels of circulating tumor DNA (ctDNA) before treatment and an early increase during treatment were linked to better outcomes, indicating that ctDNA can be a useful biomarker for predicting treatment response.

The study found that ctDNA levels correlated well with imaging biomarkers from MRI and FDG-PET scans, suggesting that ctDNA and imaging metrics are similarly effective in predicting freedom from progression after chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early HPV ctDNA Kinetics and Imaging Biomarkers Predict Therapeutic Response in p16+ Oropharyngeal Squamous Cell Carcinoma. Cao, Y., Haring, CT., Brummel, C., et al.[2022]

In a study of 39 patients with unexplained symptoms suggestive of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), circulating tumor tissue-modified viral (TTMV-HPV) DNA was detected in 2 patients, both of whom were later diagnosed with HPV-positive OPSCC, indicating the test's potential for early diagnosis.

The TTMV-HPV DNA testing was perceived as helpful by 68% of clinicians in decision-making and 86% believed it would be useful for future patients, suggesting its feasibility as a diagnostic aid, although a negative result does not rule out the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study. Batool, S., Sethi, RKV., Wang, A., et al.[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]

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Even the rates of treatment-related grade ≥2 adverse events (AEs) were similar, with more neutropenia, constipation, and tinnitus in the RT arm and more trismus ...

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