P53 Mutational Status and cf HPV DNA for the Management of HPV-associated OPSCC

September 13, 2023 updated by: UNC Lineberger Comprehensive Cancer Center

LCCC 1612: P53 Mutational Status and Circulating Free HPV DNA for the Management of HPV-associated Oropharyngeal Squamous Cell Cancers

The primary objective of this study is to evaluate whether genomic based risk-stratification can be used in deciding whether to de-intensify in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) with > 10 pack years smoking history. Hypothesis: Patients with HPV-associated OPSCC, > 10 pack years smoking history, and non-mutated p53 will have similar 2 year progression-free survival (PFS) as patients with < 10 pack years smoking history.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The proposed study is a follow-up study to LCCC 1120 and 1413. The investigators have shown that de-intensification is efficacious in these two phase II studies. A major question is whether the investigators can de-intensify in patients with HPV-associated oropharyngeal cancer who have smoking histories. The investigators' hypothesis is that genomic profiling of patients' tumors (specifically for p53 mutations) will help in triaging patients to de-intensification versus standard of care. Patients with HPV-associated OPSCC will be enrolled regardless of smoking history and p53 mutational status will be assessed in patients with a smoking history. The investigators will use the same de-intensification chemoradiotherapy regimen already evaluated in LCCC 1120 and 1413 in patients with HPV-associated OPSCC who have a minimal smoking history and in patients with a smoking history but with wild-type p53. Patients with a smoking history who have mutated p53 will not receive de-intensified chemoradiotherapy, but instead will receive standard doses. The hypothesis is that by using genomics in the patients with a significant smoking history, the investigators will better select those who can be safely de-intensified. Circulating free HPV DNA (cf-HPV-DNA) will also be prospectively assessed from blood samples.

Study Type

Interventional

Enrollment (Actual)

215

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Jacksonville, Florida, United States, 32206
        • University of Florida Proton Therapy Institute
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill, Department of Radiation Oncology
      • Raleigh, North Carolina, United States, 27607
        • Rex Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥ 18 years of age (no upper age limit)
  2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
  3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
  4. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
  5. ECOG Performance Status 0-1
  6. CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl
  7. Adequate renal and hepatic function within 4 weeks prior to treatment, defined as follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN; AST or ALT < 3 x the institutional ULN
  8. Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
  9. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
  10. Patients must be deemed able to comply with the treatment plan and follow-up schedule.
  11. Patients must provide study specific informed consent prior to study entry

Exclusion Criteria:

  1. Prior history of radiation therapy to the head and neck
  2. Prior history of head and neck cancer.
  3. Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
  4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
  5. 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 or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation parameters are not required for entry into this protocol); Pre-existing ≥ grade 2 neuropathy; Prior organ transplant; Systemic lupus; Psoriatic arthritis
  6. Known HIV positive.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ≤ 10 pack years smoking history
Radiation: Intensity Modulated Radiotherapy (IMRT) - deintensified
60 Gy at 2 Gy/fx
Drug: Cisplatin (or alternative) - deintensified
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses.
Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Experimental: > 10 py smoking history, no p53 mutation
Radiation: Intensity Modulated Radiotherapy (IMRT) - deintensified
60 Gy at 2 Gy/fx
Drug: Cisplatin (or alternative) - deintensified
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses.
Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Active Comparator: > 10 py smoking history, p53 mutation
Procedure: Assessment for surgical evaluation
Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Radiation: Intensity Modulated Radiotherapy (IMRT) - standard
70 Gy at 2 Gy/fx
Drug: Cisplatin (or alternative) - standard
The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 7 total doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
2 year Progression Free Survival after de-intensified chemoradiation therapy (CRT) in HPV-associated OPSCC
Time Frame: Two years after completion of CRT on last enrolled patient
Two years after completion of CRT on last enrolled patient

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in plasma circulating free HPV DNA during and after treatment as related to clinical outcomes in patients with HPV-associated OPSCC
Time Frame: Two years after completion of CRT on last enrolled patient
Two years after completion of CRT on last enrolled patient
Local control rate
Time Frame: 2 years post-CRT
2 years post-CRT
Regional control rate
Time Frame: 2 years post-CRT
2 years post-CRT
Local-regional control rate
Time Frame: 2 years post-CRT
2 years post-CRT
Distant metastasis free survival
Time Frame: 2 years post-CRT
2 years post-CRT
Overall survival rate
Time Frame: 2 years post-CRT
2 years post-CRT
Head and neck quality of life assessments
Time Frame: From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years
From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years
Speech and swallowing function via penetration-aspiration scale (PAS) and EAT-10 survey assessments
Time Frame: From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years
From date of study enrollment to last follow-up as long as patient continues seeing study doctor, up to 30 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Investigators

  • Principal Investigator: Wendell Gray Yarbrough, MD, University of North Carolina at Chapel Hill, Department of Radiation Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

August 1, 2023

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

January 30, 2017

First Submitted That Met QC Criteria

March 6, 2017

First Posted (Actual)

March 10, 2017

Study Record Updates

Last Update Posted (Actual)

September 14, 2023

Last Update Submitted That Met QC Criteria

September 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC1612

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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