Study of De_Intensified Postoperative Radiation Therapy for HPV Associated Oropharyngeal Squamous Cell Carcinoma

NCT ID: NCT03875716

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2027-12-31

Brief Summary

This research study is studying lowering the standard dose of radiation and chemotherapy after surgery, to minimize the side effects and improve the quality of life.

Detailed Description

This research study is being done to study if less intensive treatments can be used after surgery for head and neck cancers that are due to the human papilloma virus (HPV). In general, these cancers have better cure rates than other types of head and neck cancers. Therefore, the investigators are studying whether we can safely reduce the amount of treatment after surgery, such as surveillance (instead of using radiation) or less radiation or less chemotherapy, while maintaining good cure rates. The investigators hope that by reducing the intensity of treatment, this will lead to less side effects during and after cancer treatment.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Risk

Observation without adjuvant therapy

• Pathologic T0-2, N0-1
• Minimum of 15 lymph nodes retrieved on neck dissection per dissected side of the neck
• Single positive lymph node up to 3cm
• No extranodal extension
• Clear margins
• Undetectable postoperative circulating tumor HPV DNA

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Radiation therapy

Intermediate Risk

Reduced-dose radiation (46Gy)

• Pathologic T0-2N0-2 and any one of the following features:
• 2 or more positive lymph nodes
• single node >3cm
• <15 lymph nodes retrieved on neck dissection for each side of the neck
• Positive lymph nodes in level IB, IV, or V

-≤1mm extranodal extension

• Positive lymph node(s) contralateral to the primary tumor
• Close margins
• Detectable postoperative circulating tumor HPV DNA

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Radiation therapy

High Risk

Postoperative radiation (60Gy) without chemotherapy

• Pathologic T0-4N0-2 and any one of the following features:

->1mm extranodal extension

• Microscopic positive margins

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Radiation therapy

Interventions

Radiation therapy

Radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed squamous cell carcinoma of the tonsil or base of tongue (oropharynx) or unknown primary with p16-positive cervical lymph node metastases
• HPV-associated tumor as defined by: positive p16 immunohistochemistry (>70%) OR in situ hybridization OR PCR-based methods
• Eligible for curative-intent surgery with anticipated negative margins
• Surgery performed at Brigham & Women's Hospital
• Age 18 or older years.
• ECOG performance status 0-1 (Karnofsky ≥70%, see Appendix A)
• Normal organ and marrow function as defined below:

• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine ≤ 1.5 times the institutional upper limit of normal OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• Patients with ≤20 pack-years of cumulative cigarette smoking. Pack-years are calculated by multiplying the number of years smoked with the pack of cigarettes smoked per day. One pack is considered to contain 20 cigarettes.
• Tumor clinical stage (AJCC 8th edition): T0 or T1 or T2
• Nodal clinical stage (AJCC 8th edition): N0 or N1
• No distant metastases. Clinical M-stage must be M0 (AJCC 8th edition).
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Prior history of head and neck cancer within 5 years.
• Prior head and neck radiation
• Clinically fixed or matted nodes
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Note: that HIV positive patients will be eligible.
• Pregnant women are excluded from this study because of the teratogenic risks of radiation exposure to the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with radiation therapy and supportive care medications required for symptomatic management of head and neck cancer side effects as well as general anesthesia required for oncologic head and neck surgery, breastfeeding should be discontinued if the mother is enrolled in the study. Pregnancy status will be determined by a serum pregnancy test.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Danielle Margalit, MD, MPH

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Danielle N. Margalit, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Danielle N. Margalit, MD, MPH

Role: CONTACT

dmargalit@lroc.harvard.edu

617-632-6817

Facility Contacts

Danielle N. Margalit, MD, MPH

Role: primary

danielle_margalit@dfci.harvard.edu

617-632-3591

Other Identifiers

19-009

Identifier Type: -

Identifier Source: org_study_id