A Study on Using Cell-Free Tumor DNA (ctDNA) Testing to Decide When to StartRoutine Treatment in People With Human Papilloma Virus (HPV)- Associated Oropharynx Cancer (OPC)

Launched by MEMORIAL SLOAN KETTERING CANCER CENTER · Mar 24, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating whether measuring levels of cell-free tumor DNA (ctDNA) from the human papillomavirus (HPV) can help doctors decide when to start routine treatments for patients with HPV-related oropharyngeal cancer, a type of throat cancer. The study has two parts: in one part, researchers will look at whether tracking ctDNA levels can safely identify patients who may not need radiation therapy right after surgery, allowing it to be delayed until signs of cancer reappear. In the other part, the aim is to see if patients who usually require 6 weeks of combined chemotherapy and radiation can safely receive a shorter treatment of only 3 weeks based on their ctDNA results.

To participate in the trial, patients must be at least 18 years old and have been diagnosed with HPV-16 oropharyngeal cancer. They should have already had surgery to remove the visible cancer and should have specific levels of ctDNA detected in their blood. Patients enrolled in this study can expect close monitoring and testing of their ctDNA levels, which will help doctors tailor their treatments more effectively. It's important to know that this trial is actively recruiting participants, and those interested should discuss their eligibility with their healthcare provider.

Gender

ALL

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.