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

Primary Purpose

Head and Neck Cancer

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Radiation therapy
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer

Eligibility Criteria

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

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.

Sites / Locations

  • Dana Farber Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Low Risk

Intermediate Risk

High Risk

Arm Description

Observation without adjuvant therapy Pathologic T0-2, N0-1 Minimum of 15 lymph nodes retrieved on neck dissection per dissected side of the neck -≤2 positive lymph nodes confined to level II and/or level III No extranodal extension Clear margins

Reduced-dose radiation (46Gy) Pathologic T0-2N0-2 and any one of the following features: ->2 positive lymph nodes <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

Postoperative radiation (60Gy) without chemotherapy Pathologic T0-4N0-2 and any one of the following features: ->1mm extranodal extension Microscopic positive margins

Outcomes

Primary Outcome Measures

Disease-free survival
Survival without any signs or symptoms of cancer after the treatment ends.

Secondary Outcome Measures

Overall Survival
The length of time from the start of treatment until death.
Toxicity Rate
Adverse events experienced by the participants.
Quality Of Life Questionnaire
Assesses the physical; social/family; emotional and functional wellbeing, using Functional Assessment of Cancer Therapy for Head and Neck (FACT-H&N) on a scale of 0-4 (where 0 indicates the lowest quality of life and 4 indicates the highest quality of life).
Symptom burden:
Patient-reported symptom severity, using M.D. Anderson Symptom Inventory - Head & Neck (MDASI-HN) on a scale of 0-10 (where 0 indicates symptom is not present and 10 indicates the symptom is as bad as can be)
Dysphagia
Swallowing ability or difficulty. Dysphagia-related quality of life, assessed with the MD Anderson Dysphagia Inventory (MDADI) on a scale of 1-5 (where 1 indicates the patient strongly agrees and 5 indicates the patient strongly disagrees)
Shoulder dysfunction
Shoulder function or dysfunction is measured with the "neck dissection impairment index" (NDII). This evaluates how much the patient's neck and/or shoulder affects them as a result of the treatment they received in their neck during the overall management of their cancer. This scale goes from 1-5 (1 being "not at all" and 5 being "a lot")

Full Information

First Posted
March 13, 2019
Last Updated
February 24, 2023
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03875716
Brief Title
Study of De_Intensified Postoperative Radiation Therapy for HPV Associated Oropharyngeal Squamous Cell Carcinoma
Official Title
A Phase 2 Study of De-Intensified Risk-Adapted Postoperative Radiation Therapy for Human Papilloma Virus Associated Oropharyngeal Squamous Cell Carcinoma: the ADAPT Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2019 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
111 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Risk
Arm Type
Experimental
Arm Description
Observation without adjuvant therapy Pathologic T0-2, N0-1 Minimum of 15 lymph nodes retrieved on neck dissection per dissected side of the neck -≤2 positive lymph nodes confined to level II and/or level III No extranodal extension Clear margins
Arm Title
Intermediate Risk
Arm Type
Experimental
Arm Description
Reduced-dose radiation (46Gy) Pathologic T0-2N0-2 and any one of the following features: ->2 positive lymph nodes <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
Arm Title
High Risk
Arm Type
Experimental
Arm Description
Postoperative radiation (60Gy) without chemotherapy Pathologic T0-4N0-2 and any one of the following features: ->1mm extranodal extension Microscopic positive margins
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Radiation therapy
Primary Outcome Measure Information:
Title
Disease-free survival
Description
Survival without any signs or symptoms of cancer after the treatment ends.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
The length of time from the start of treatment until death.
Time Frame
2 years
Title
Toxicity Rate
Description
Adverse events experienced by the participants.
Time Frame
2 years
Title
Quality Of Life Questionnaire
Description
Assesses the physical; social/family; emotional and functional wellbeing, using Functional Assessment of Cancer Therapy for Head and Neck (FACT-H&N) on a scale of 0-4 (where 0 indicates the lowest quality of life and 4 indicates the highest quality of life).
Time Frame
2 Years
Title
Symptom burden:
Description
Patient-reported symptom severity, using M.D. Anderson Symptom Inventory - Head & Neck (MDASI-HN) on a scale of 0-10 (where 0 indicates symptom is not present and 10 indicates the symptom is as bad as can be)
Time Frame
2 years
Title
Dysphagia
Description
Swallowing ability or difficulty. Dysphagia-related quality of life, assessed with the MD Anderson Dysphagia Inventory (MDADI) on a scale of 1-5 (where 1 indicates the patient strongly agrees and 5 indicates the patient strongly disagrees)
Time Frame
2 Years
Title
Shoulder dysfunction
Description
Shoulder function or dysfunction is measured with the "neck dissection impairment index" (NDII). This evaluates how much the patient's neck and/or shoulder affects them as a result of the treatment they received in their neck during the overall management of their cancer. This scale goes from 1-5 (1 being "not at all" and 5 being "a lot")
Time Frame
2 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Danielle N. Margalit, MD, MPH
Phone
617-632-6817
Email
dmargalit@lroc.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danielle N. Margalit, MD, MPH
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02062
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danielle N. Margalit, MD, MPH
Phone
617-632-3591
Email
danielle_margalit@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Danielle N. Margalit, MD, MPH

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication.
IPD Sharing Access Criteria
BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Learn more about this trial

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

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