NCT03077243

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
195

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_2

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 30, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 10, 2017

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 14, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 14, 2022

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

May 2, 2024

Completed
Last Updated

May 2, 2024

Status Verified

April 1, 2024

Enrollment Period

6 years

First QC Date

January 30, 2017

Results QC Date

November 6, 2023

Last Update Submit

April 5, 2024

Conditions

Keywords

Human PapillomavirusOropharynxOropharyngeal Squamous Cell CarcinomaSquamous Cell CarcinomaRadiation TherapyChemotherapyp16

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS)

    PFS was assessed as the time from the first day of chemoradiation therapy (CRT) until disease progression. Disease progression was defined as biopsy proven tumor cells. Positron emission tomography / computerized tomography (PET/CT) was performed at week 10-16 (optimally at week 12) after completion of therapy. Biopsies were performed for subjects with imaging or clinical exam results suspicious for tumor. Clinical follow-up occurred and chest imaging was performed during the follow-up.

    Two years after completion of the treatment

Secondary Outcomes (9)

  • Number of Participants With Plasma Circulating Free DNA -Baseline

    Baseline

  • Number of Participants With Plasma Circulating Free DNA -3months

    3 months after completion of the treatment

  • Number of Participants With Plasma Circulating Free DNA -1 Year

    1 year after completion of the treatment

  • Number of Participants With Plasma Circulating Free DNA -2 Year

    2 years after completion of the treatment

  • Local Control Rate

    2 years after completion of the treatment

  • +4 more secondary outcomes

Study Arms (1)

Radiotherapy and/or chemotherapy.

EXPERIMENTAL

Subjects with Oropharyngeal Squamous Cell Carcinoma receiving radiotherapy and/or chemotherapy.

Radiation: Intensity Modulated Radiotherapy (IMRT)Drug: Cisplatin (or alternative)Procedure: Assessment for surgical evaluation

Interventions

60- 70 Gy at 2 Gy/fx

Radiotherapy and/or chemotherapy.

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 -7 total doses.

Radiotherapy and/or chemotherapy.

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.

Radiotherapy and/or chemotherapy.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Florida Proton Therapy Institute

Jacksonville, Florida, 32206, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

Rex Healthcare

Raleigh, North Carolina, 27607, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Carcinoma, Squamous CellHead and Neck NeoplasmsOropharyngeal NeoplasmsSquamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy, Intensity-ModulatedCisplatinRestraint, Physical

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, Squamous CellNeoplasms by SitePharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, ConformalRadiotherapy, Computer-AssistedRadiotherapyTherapeuticsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsBehavior ControlImmobilizationInvestigative Techniques

Limitations and Caveats

Research at two study sites terminated early. Each site collected and stored the research data for its participants in its own systems. The validity of existing, sequestered outcome data from sites 3 and 4 cannot be confirmed and may not be reliable. Therefore, arm/group and follow-up data related to sixty-nine subjects are not included in the data tables.

Results Point of Contact

Title
Melahat G. Canter MD MS Clinical Trial Analyst
Organization
University of North Carolina Lineberger Comprehensive Cancer Center

Study Officials

  • Wendell Gray Yarbrough, MD

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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2017

First Posted

March 10, 2017

Study Start

December 1, 2016

Primary Completion

December 14, 2022

Study Completion

December 14, 2022

Last Updated

May 2, 2024

Results First Posted

May 2, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations