Clinical trial NCT03077243: P53 Mutational Status and cf HPV DNA for the Management of HPV-associated OPSCC
Official title: LCCC 1612: P53 Mutational Status and Circulating Free HPV DNA for the Management of HPV-associated Oropharyngeal Squamous Cell Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Keywords: Human Papillomavirus
Oropharynx
Oropharyngeal Squamous Cell Carcinoma
Squamous Cell Carcinoma
Radiation Therapy
Chemotherapy
p16
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2017-03-10
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Two years after completion of the treatment
Secondary outcomes:
measure: Number of Participants With Plasma Circulating Free DNA -Baseline
timeFrame: Baseline
measure: Number of Participants With Plasma Circulating Free DNA -3months
timeFrame: 3 months after completion of the treatment
measure: Number of Participants With Plasma Circulating Free DNA -1 Year
timeFrame: 1 year after completion of the treatment
measure: Number of Participants With Plasma Circulating Free DNA -2 Year
timeFrame: 2 years after completion of the treatment
measure: Local Control Rate
timeFrame: 2 years after completion of the treatment
measure: Regional Control Rate
timeFrame: 2 years post-CRT
measure: Local-regional Control Rate
timeFrame: 2 years after completion of the treatment
measure: Distant Metastasis Free Survival
timeFrame: Two years after completion of the treatment
measure: Overall Survival Rate
timeFrame: Up to 2 years after completion of treatment
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Proton Therapy Institute
state: Florida
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, Department of Radiation Oncology
state: North Carolina
city: Raleigh
country: United States
facility: Rex Healthcare
state: North Carolina
Study officials:
affiliation: University of North Carolina at Chapel Hill, Department of Radiation Oncology
name: Wendell Gray Yarbrough, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chera BS, Kumar S, Shen C, Amdur R, Dagan R, Green R, Goldman E, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Blumberg J, Patel S, Thorp B, Weissler M, Yarbrough W, Sheets N, Mendenhall W, Tan XM, Gupta GP. Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. J Clin Oncol. 2020 Apr 1;38(10):1050-1058. doi: 10.1200/JCO.19.02444. Epub 2020 Feb 4.