Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC

• ClinicalTrials.gov Identifier: NCT04564989
• Recruitment Status: Recruiting
• First Posted: September 25, 2020
• Last Update Posted: April 17, 2024
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Mayo Clinic; National Institute of Dental and Craniofacial Research (NIDCR)
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

Tracking Information

• First Submitted Date: August 14, 2020
• First Posted Date: September 25, 2020
• Last Update Posted Date: April 17, 2024
• Actual Study Start Date: November 19, 2020
• Estimated Primary Completion Date: November 2033 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2020)

• Recurrence of OPSCC [ Time Frame: From date of therapy completion until biopsy-proven recurrence, assessed up to 5 years ]
  Patients will undergo post-treatment CT scans per institutional standard of care to detect cancer recurrence. Status of recurrence of OPSCC will be confirmed based on biopsy.
• Progression-free survival [ Time Frame: From beginning or end of treatment until date of CT-detected recurrence or date of death, assessed up to 5 years ]
  Time-to-recurrence will be defined as time lapsed from end (or start) of treatment to first date recurrence (biopsy proven occur later) is detected by CT scans, or death. Otherwise, time-to-recurrence is censored at end of study date.
• Positive Predictive Value [ Time Frame: Baseline to up to 5 years ]
  Positive Predictive Value (PPV) is defined as probability that patients with two consecutive positive cHPVDNA (i.e., detectable cHPVDNA) really develop OPSCC recurrence during the study period.
• Negative Predictive Value [ Time Frame: Baseline to up to 5 years ]
  Negative Predictive Value (NPV) is defined as probability that patients without two consecutive positive cHPVDNA do not develop OPSCC recurrence during the study period.
• Quality of Life questionnaire [ Time Frame: Baseline until recurrence or up to 5 years ]
  At specified timepoints before, during, and after treatment, patients will complete a questionnaire comprised of questions from the European Organization for Research and Treatment of Cancer (EORTC) QLQ H&N35, which is for head and neck cancer patients, and EORTC QLQ C30, which is a general cancer assessment.

Original Primary Outcome Measures (submitted: September 24, 2020)

• Recurrence of OPSCC [ Time Frame: From date of therapy completion until biopsy-proven recurrence, assessed up to 5 years ]
  Patients will undergo post-treatment CT scans per institutional standard of care to detect cancer recurrence. Status of recurrence of OPSCC will be confirmed based on biopsy.
• Progression-free survival [ Time Frame: From beginning or end of treatment until date of CT-detected recurrence or date of death, assessed up to 5 years ]
  Time-to-recurrence will be defined as time lapsed from end (or start) of treatment to first date recurrence (biopsy proven occur later) is detected by CT scans, or death. Otherwise, time-to-recurrence is censored at end of study date.
• Positive Predictive Value [ Time Frame: Baseline to up to 5 years ]
  Positive Predictive Value (PPV) is defined as probability that patients with two consecutive positive cHPVDNA (i.e., detectable cHPVDNA) really develop OPSCC recurrence during the study period.
• Negative Predictive Value [ Time Frame: Baseline to up to 5 years ]
  Negative Predictive Value (NPV) is defined as probability that patients without two consecutive positive cHPVDNA do not develop OPSCC recurrence during the study period.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC
• Official Title: LCCC 2044: Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC
• Brief Summary: The primary goal of this study is to examine whether recurrence of HPV-associated OPSCC can be predicted by two factors: 1) mutations in genes called TRAF3 and CYLD, and 2) measurements of circulating HPV DNA in blood plasma. The study will also investigate whether HPV integration is associated with TRAF3 and CYLD mutations, and whether recurrence prediction improves when looking at HPV integration along with TRAF3 and CYLD mutations.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with HPV+ oropharyngeal squamous cell carcinoma who will receive definitive cancer treatment.

Condition

• Oropharyngeal Squamous Cell Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Oropharynx Squamous Cell Carcinoma

• Intervention: Not Provided

Study Groups/Cohorts

HPV+ OPSCC Patients

Patients with p16+ squamous cell carcinoma of the oropharynx (or unknown primary) who will receive definitive cancer treatment.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 24, 2020): 220
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2033
• Estimated Primary Completion Date: November 2033 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ≥ 18 years of age
• T0-T2 N2a-N3 M0 or T3-T4 N0-N3 M0 (AJCC 7th edition)
• Biopsy proven squamous cell carcinoma of the oropharynx or unknown primary
• No prior therapy
• No evidence of distant metastatic disease
• p16 positive = diffuse ≥ 70% tumor cell expression, with at least moderate (2/3+) staining intensity
• Planned for receipt of definitive cancer treatment
• ECOG Performance Status 0-1
• Patients must be deemed able to comply with the treatment plan and follow-up schedule.
• Patients must provide study specific informed consent prior to study entry

Exclusion Criteria: All subjects meeting any of the exclusion criteria at baseline will be excluded from study participation:

• Prior history of radiation therapy to the head and neck
• Prior history of head and neck cancer.
• Inadequate pre-treatment tissue sample for tumor genomic analyses

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chris Hilliard; 919-966-4432; chris_hilliard@med.unc.edu

Contact: Wendell Yarbrough, MD; 919-843-7091; dell@med.unc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04564989
• Other Study ID Numbers: LCCC 2044; 1U01DE029754-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: UNC Lineberger Comprehensive Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: UNC Lineberger Comprehensive Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• Mayo Clinic
• National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Principal Investigator: Wendell Yarbrough, MD; UNC Chapel Hill

• PRS Account: UNC Lineberger Comprehensive Cancer Center
• Verification Date: March 2024