Using blood tests to determine treatment timing for HPV-related throat cancer

Phase II Trial Evaluating Selective Minimal Residual Disease Directed Adjuvant Radiation in Human Papilloma Virus Associated Oropharynx Carcinoma

This study is testing if blood tests can help decide when to start treatment for people with HPV-related throat cancer after surgery, by checking their tumor DNA levels.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 8 sites (Miami, Florida and 7 other locations)
• Trial ID: NCT05307939 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of monitoring cell-free tumor DNA (ctDNA) levels in patients with HPV-associated oropharyngeal cancer (OPC) to assess cancer relapse risk. Participants will either have recently undergone surgery or be scheduled for it. The study has two arms: one aims to identify patients who can safely delay radiation therapy based on ctDNA levels, while the other seeks to determine if some patients can receive a shorter course of chemoradiation therapy. The approach utilizes advanced HPV ctDNA testing to guide treatment decisions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with HPV-16 positive oropharyngeal squamous cell carcinoma who have undergone surgical resection.

Not a fit: Patients with HPV-negative oropharyngeal cancer or those who do not meet the specific eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized treatment plans for patients with HPV-related throat cancer, potentially reducing unnecessary radiation therapy.

How similar studies have performed: Other studies have shown promise in using ctDNA for monitoring cancer, suggesting this approach may be effective, though this specific application is novel.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18
* ECOG 0-2
* HPV-16 squamous cell carcinoma of the oropharynx or HPV-16 head and neck squamous cell carcinoma of unknown primary . HPV status must be confirmed by in-situ hybridization.
* HPV ctDNA detectable by HPV digital PCR (Naveris assay) with a minimum of 50 copies/mL pre-operatively.
* Surgical resection of all gross disease with no gross disease visualized on post-operative imaging.

  o For patients with pT0 (unknown primary) evaluation for the primary should include PET/CT, direct laryngoscopy, ipsilateral tonsillectomy, and targeted biopsy. This should be followed by a neck dissection.
* Two, undetectable (\<1 copy/mL) post-operative HPV ctDNA within 2-6 weeks following surgery (blood drawn at least one week apart preferred).
* A minimum of one of the following pathologic criteria: (Arm A)

  * AJCC 7 Stage: pT0N1-N2b, pT1N1, pT2N1, or ≥pT3
  * AJCC 7 ≥pN2
  * Lymphovascular invasion
  * Perineural invasion
  * Close pathologic margin (≤ 3 mm)
* Signed informed consent form by the participant or their legally authorized representative (LAR).
* A minimum of one of the following pathologic criteria (Arm B):

  * Microscopic positive margin
  * Extracapsular extension
* Signed informed consent form by the participant or their legally authorized representative (LAR).

Additional criteria for Arm B only:

* Adequate hematologic function within 30 days prior to registration, defined as follows:

  * White Blood Count (WBC) ≥ 2 K/mcL
  * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
  * Platelets ≥ 100,000 cells/mm3
  * Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
* Adequate renal function within 30 days prior to registration, defined as follows:

  * Serum creatinine \< 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:
  * CCr male = \[(140 - age) x (wt in kg)\] divided by \[(Serum Cr mg/dl) x (72)\]
  * CCr female = 0.85 x (CrCl male)
* Adequate hepatic function within 30 days prior to registration, defined as follows:

  \- Bilirubin \< 2 mg/dl o AST or ALT \< 3 x the upper limit of normal
* Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential

Exclusion Criteria:

* Metastatic disease
* Non-HPV16 genotype (i.e. HPV-18,-31, -33, -35)
* Patients who receive surgery at outside institution. Exceptions can be made for high-volume surgical centers at the discretion of the PI/co-PI
* Prior head and neck radiation
* Patients without pre-operative HPV ctDNA or pre-operative HPV ctDNA ≤ 50 copies/mL
* Subjects with simultaneous primary cancers outside of the oropharynx

  o Note: Exceptions can be made for patients with simultaneous primaries outside of the oropharynx if determined by the PI/Co-PI, then the patient can proceed with protocol activities
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years is 90% or greater

  o Note: Exceptions can be made for patients with prior invasive malignancy if determined by the PI/Co-PI, then the patient can proceed with protocol activities
* Prior systemic chemotherapy for the study cancer

  o Note: prior chemotherapy for a different cancer is allowable
* 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.

Where this trial is running

Miami, Florida and 7 other locations

• Baptist Alliance MCI (Data Collection Only) — Miami, Florida, United States (Recruiting)
• Memorial Sloan Kettering Basking Ridge (Limited protocol activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activites) — East White Plains, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited protocol activities) — Rockville Centre, New York, United States (Recruiting)

Study contacts

• Principal investigator: Acharf Shamseddine, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Acharf Shamseddine, MD

Conditions HPV; Oropharynx Cancer; HPV-Related Carcinoma; HPV-Related Malignancy; HPV Positive Oropharyngeal Squamous Cell Carcinoma; ctDNA; NavDx test; 21-434