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

Primary Purpose

Carcinoma, Squamous Cell, Head and Neck Neoplasms, Oropharyngeal Neoplasms

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Intensity Modulated Radiotherapy (IMRT) - deintensified

Intensity Modulated Radiotherapy (IMRT) - standard

Cisplatin (or alternative) - deintensified

Cisplatin (or alternative) - standard

Assessment for surgical evaluation

About this trial

This is an interventional treatment trial for Carcinoma, Squamous Cell focused on measuring Human Papillomavirus, Oropharynx, Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, Radiation Therapy, Chemotherapy, p16

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 18 years of age (no upper age limit)
T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
ECOG Performance Status 0-1
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
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
Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
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:

Prior history of radiation therapy to the head and neck
Prior history of head and neck cancer.
Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
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
Known HIV positive.

Sites / Locations

University of Florida
University of Florida Proton Therapy Institute
University of North Carolina at Chapel Hill, Department of Radiation Oncology
Rex Healthcare

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

≤ 10 pack years smoking history

> 10 py smoking history, no p53 mutation

> 10 py smoking history, p53 mutation

Arm Description

Outcomes

Primary Outcome Measures

2 year Progression Free Survival after de-intensified chemoradiation therapy (CRT) in HPV-associated OPSCC

Secondary Outcome Measures

Changes in plasma circulating free HPV DNA during and after treatment as related to clinical outcomes in patients with HPV-associated OPSCC

Local control rate

Regional control rate

Local-regional control rate

Distant metastasis free survival

Overall survival rate

Head and neck quality of life assessments

Speech and swallowing function via penetration-aspiration scale (PAS) and EAT-10 survey assessments

Full Information

NCT ID

NCT03077243

First Posted

January 30, 2017

Last Updated

September 13, 2023

Sponsor

UNC Lineberger Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT03077243

Brief Title

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 2016 (Actual)

Primary Completion Date

August 2023 (Actual)

Study Completion Date

February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNC Lineberger Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Squamous Cell, Head and Neck Neoplasms, Oropharyngeal Neoplasms

Keywords

Human Papillomavirus, Oropharynx, Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, Radiation Therapy, Chemotherapy, p16

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

215 (Actual)

8. Arms, Groups, and Interventions

Arm Title

≤ 10 pack years smoking history

Arm Type

Experimental

Arm Title

> 10 py smoking history, no p53 mutation

Arm Type

Experimental

Arm Title

> 10 py smoking history, p53 mutation

Arm Type

Active Comparator

Intervention Type

Radiation

Intervention Name(s)

Intensity Modulated Radiotherapy (IMRT) - deintensified

Intervention Description

60 Gy at 2 Gy/fx

Intervention Type

Radiation

Intervention Name(s)

Intensity Modulated Radiotherapy (IMRT) - standard

Intervention Description

70 Gy at 2 Gy/fx

Intervention Type

Drug

Intervention Name(s)

Cisplatin (or alternative) - deintensified

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Cisplatin (or alternative) - standard

Intervention Description

Intervention Type

Procedure

Intervention Name(s)

Assessment for surgical evaluation

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

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

Title

Local control rate

Time Frame

2 years post-CRT

Title

Regional control rate

Time Frame

2 years post-CRT

Title

Local-regional control rate

Time Frame

2 years post-CRT

Title

Distant metastasis free survival

Time Frame

2 years post-CRT

Title

Overall survival rate

Time Frame

2 years post-CRT

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 18 years of age (no upper age limit) T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment ECOG Performance Status 0-1 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 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 Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment. 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: Prior history of radiation therapy to the head and neck Prior history of head and neck cancer. Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves) Currently taking Disease Modifying Rheumatoid Drugs (DMRDs) 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 Known HIV positive.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wendell Gray Yarbrough, MD

Organizational Affiliation

University of North Carolina at Chapel Hill, Department of Radiation Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

Facility Name

University of Florida Proton Therapy Institute

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32206

Country

United States

Facility Name

University of North Carolina at Chapel Hill, Department of Radiation Oncology

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Rex Healthcare

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27607

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

32017652

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. Erratum In: J Clin Oncol. 2020 Oct 20;38(30):3579. J Clin Oncol. 2023 Sep 20;41(27):4449.

Results Reference

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

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