What is the mechanism of action of this treatment?

The most common treatments for Oropharyngeal Carcinoma (OPC) include radiation therapy (RT), chemoradiation therapy (CRT), and emerging biomarker-based monitoring like HPV ctDNA. RT uses high-energy radiation to kill cancer cells by damaging their DNA, while CRT combines RT with chemotherapy agents like cisplatin to enhance the cancer-killing effects. The use of HPV ctDNA as a biomarker allows for the detection of minimal residual disease and early relapse, potentially guiding the timing and intensity of treatment. These mechanisms are crucial for OPC patients as they offer targeted, effective treatment options and personalized monitoring, which can improve outcomes and reduce unnecessary treatment-related toxicity.

What side effects are associated with this type of intervention?

The most common treatments for Oropharyngeal Carcinoma (OPC) include surgery, radiation therapy (RT), and concurrent chemoradiation therapy (CRT) with agents such as cisplatin, carboplatin, and cetuximab. Known side effects of these treatments include acute toxicities like nausea, vomiting, pain, and appetite loss. Radiation therapy can cause skin changes, radiation pneumonitis, esophagitis, and cardiovascular issues. Chemotherapy, particularly with cisplatin, can lead to neuropathy, hearing loss, and nephrotoxicity. Cetuximab is associated with severe skin reactions, hypomagnesemia, and infusion-related reactions. These side effects can significantly impact the quality of life for patients undergoing treatment.

What prior FDA approvals exist?

Pembrolizumab and nivolumab are two PD-1 inhibitors that have received FDA approval for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), which includes oropharyngeal carcinoma (OPC). Pembrolizumab was approved for patients with disease progression on or after platinum-containing chemotherapy, providing a new treatment option for this patient population. Similarly, nivolumab has been approved for use in patients with recurrent or metastatic HNSCC who have progressed after platinum-based chemotherapy. These approvals are significant as they offer targeted immunotherapy options for patients with advanced stages of the disease.

What other types of research exist?

One promising alternative to HPV ctDNA monitoring for OPC patients is the use of PD-L1 expression as a biomarker. PD-L1 expression is utilized as a predictive biomarker of response to immune checkpoint inhibitors (ICIs) in multiple tumor histologies, including head and neck cancers. Another potential alternative is the use of gene expression assays, which can provide unique information regarding biologic risk and natural history in cancers. These methods are being increasingly validated and could offer effective monitoring and treatment response evaluation for OPC patients.

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CombinationProduct

ctDNA Testing for Oropharyngeal Cancer

Phase 2

Recruiting

Led By Linda Chen, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A minimum of one of the following pathologic criteria (Arm B): - Microscopic positive margin - Extracapsular extension

ECOG 0-2

Must not have

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.

Metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a blood test to detect tiny pieces of HPV DNA in people with throat cancer who have had surgery. The goal is to see if this test can help decide if and when they need more treatment like radiation or chemotherapy.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects are not explicitly listed but may include typical reactions from radiation therapy such as skin irritation, fatigue, dry mouth/throat issues; and from chemotherapy like nausea/vomiting, low blood counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am able to care for myself and move around.

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I am 18 years old or older.

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I've undergone specific tests and procedures to find the origin of my cancer, followed by surgery to remove lymph nodes in my neck.

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My cancer stage or features meet specific criteria for a study group.

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My test shows HPV DNA in my blood above 50 copies/mL.

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My surgery removed all visible cancer, and none was seen on scans after.

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My cancer is HPV-16 positive in the throat or head and neck, confirmed by a specific test.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has spread to other parts of my body.

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I have cancer in areas other than the oropharynx.

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My HPV ctDNA levels are 50 copies/mL or lower before surgery.

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My HPV type is not HPV16.

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I have received chemotherapy for my current cancer.

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I have had radiation therapy on my head or neck before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pathologically confirmed progression free survival

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Screening, active surveillance, and treatment (Arm A)Experimental Treatment6 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 Treatment6 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.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Oropharyngeal Carcinoma (OPC) include radiation therapy (RT), chemoradiation therapy (CRT), and emerging biomarker-based monitoring like HPV ctDNA. RT uses high-energy radiation to kill cancer cells by damaging their DNA, while CRT combines RT with chemotherapy agents like cisplatin to enhance the cancer-killing effects. The use of HPV ctDNA as a biomarker allows for the detection of minimal residual disease and early relapse, potentially guiding the timing and intensity of treatment. These mechanisms are crucial for OPC patients as they offer targeted, effective treatment options and personalized monitoring, which can improve outcomes and reduce unnecessary treatment-related toxicity.

Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies.Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma.[Oral cavity cancers among young people: Clinical results and prognostic analysis].