Post Operative Adjuvant Therapy De-intensification Trial for Human Papillomavirus-related, p16+ Oropharynx Cancer (ADEPT)

Adjuvant De-escalation, Extracapsular Spread, P16+, Transoral (ADEPT) Trial for Oropharynx Malignancy

This clinical trial studies the intensity of adjuvant ("helper") therapy required in p16 positive oropharynx cancer patients, who have had all known disease removed surgically by a minimally invasive approach, and who have extracapsular spread in their lymph nodes. Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways. After the surgery, receive either radiation alone, or radiation and weekly cis-platinum during therapy. Patients are then followed for cancer, functional and quality of life outcomes.

Study Overview

• Status: Terminated
• Conditions: Oropharyngeal Neoplasms
• Intervention / Treatment: Drug: Cisplatin; Radiation: Intensity-modulated radiation therapy (IMRT)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must have histologically confirmed p16 positive squamous cell carcinoma of the oropharynx (OPSCC).
• Patient must have undergone transoral resection of their T1-4a oropharynx primary to a negative margin, and a neck dissection(s).
• Patient's disease must be pathological N-stage positive.
• Patient's disease must show extracapsular spread (ECS) in their nodal metastasis verified by central pathologist's review.
• Patients with synchronous primaries are included.
• Patients with unknown primaries are included if the diagnosis and resection of a primary site in the oropharynx is made from an endoscopic or robotic surgical procedure(s).
• Patients with recent excisional node biopsies/neck dissections are included if material is evaluable for extracapsular spread.
• Patient must be ≥ 21 years of age.
• ECOG performance status ≤ 2 (Karnofsky ≥60%).

• Patients must have normal organ and marrow function as defined below:

  • leukocytes ≥3,000/mcL
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • total bilirubin <1.5 X upper normal institutional limit
  • AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal
  • creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

• Patient must not have pathologically N stage negative disease.
• Patient must not have outside nodal tissue from previous neck biopsy/neck dissections in which ECS cannot be confirmed or denied.
• Patient must not have a true unknown primary in which permanent section results are negative for malignancy in completely excised ipsilateral oropharyngeal tissue (palatine and lingual tonsil).
• Patient must not have distant metastatic disease at presentation.
• Patient must not have gross residual and/or microscopic disease present after surgery including re-resection(s), per the operative and pathology report.
• Patient must not have transoral robotic surgery (TORS) for a T3 or T4 primary tumor.
• Patient must not have a history of prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (for example, carcinoma in situ of the oral cavity, larynx, breast or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago.
• Patient must not have had previous systemic chemotherapy for the study cancer. (Note: prior chemotherapy for a different cancer is allowable).
• Patient must not be receiving any other investigational agents.
• Patient must not have had any prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patient must not have any life-threatening comorbid illnesses e.g. stroke with major sequelae or myocardial infarction/ unstable angina within the preceding 3 months or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not be pregnant or breastfeeding. If a woman of childbearing potential, patient must agree to use medically acceptable forms of contraception.

Both men and women and members of all races and ethnic groups are eligible for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy; Patients undergo postoperative IMRT once daily, 5 days a week, for 6 weeks. The prescribed radiotherapy dose will be 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions).; Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways	Radiation: Intensity-modulated radiation therapy (IMRT)
Active Comparator: Radiotherapy, cisplatin; Patients undergo postoperative IMRT once daily, 5 days a week, for 6 weeks. The prescribed radiotherapy dose will be 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions); Patients also receive cisplatin 40 mg/m2 IV on Days 1, 8, 15, 22, 29, and 36 of radiation therapy (6 doses for a total of 240 mg/m2).; Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways	Drug: Cisplatin; Other Names: CACP, CDDP, CPDD, DDP, Neoplatin; Radiation: Intensity-modulated radiation therapy (IMRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Disease-free Survival (DFS)		1 year
Locoregional Control	Rate of patients with no recurrence at original oropharyngeal site or in the neck nodal basins.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Distant Metastasis	Assessed by biopsy or imaging-detected recurrent disease at sites away from the original primary and cervical zone.	Up to 2 years
Disease Specific Survival		1 year
Number of Complications/Acute Toxicity by Organ Class	-Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Approximately 18 weeks
Change in Quality of Life as Measured by the MD Anderson Dysphagia Inventory	Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). Strongly agree = 1, Disagree = 2, No opinion = 3, Agree = 4, and Strongly Agree = 5; The lower the score the lower the quality of life	Baseline, 1 month, 6 months, 12 months, and 24 months
Change in Cognitive Function as Measured by Cognitive Failures Questionnaire	25 questions to assess the frequency in which participants experience cognitive failures including forgetfulness, distractibility, and false triggering; Answers range from 0 = never to 4 = very often; The higher the score the worse the cognitive failures the participant has experienced	Baseline, 1 month, 12 months, and 24 months
Change in Quality of Life as Measured by Neck Dissection Impairment Index (NDII)	-The NDII consists of 10 questions; each with a 5 level ordinally scaled response option ranging from "not at all" to "a lot". The response for each item is then scored from 1 to 5, with 5 denoting higher quality of life (Not at all) and 1 being the least (A lot).	Baseline, 12 months, and 24 months
Change in Quality of Life as Measured by University of Michigan Xerostomia Questionnaire	It contains 8 questions regarding dryness either during feeding or in the unstimulated state. Participants rate each item from 0 to 10, where 10 indicates the maximum dryness or discomfort due to dryness.; The higher the score the worse the participant's xerostomia	Baseline, 1 month, 6 months, 12 months, and 24 months
Change in Hearing as Measured by Hearing Handicap Inventory - Adult	11 item questionnaire to identify issues with hearing; Answers are yes = 4, sometimes = 2, and no = 0; The higher the score the more issues the participant has with hearing	Baseline, 1 month, and 12 months
Change in Quality of Life as Measured by Scale of Subjective Total Taste Acuity	1 question that asks about taste acuity; Answers are 0 = same taste acuity as before treatment; 1 = mild loss of taste acuity, but not inconvenient in daily life; moderate loss of taste acuity, and sometimes inconvenient in daily life; severe loss of taste acuity, and frequently inconvenient in daily life; and 4 = almost complete or complete loss of taste acuity; The higher the score the worse the participant's taste acuity	Baseline, 1 month, 6 months, and 12 months
Change in Quality of Life as Measured by Speech Handicap Index	31 questions regarding participant's speech and the effects of speech on his/her life; The answers for the first 30 questions range from 0 = never to 4 = always and the answers for the 31st question ranges from 0 = excellent to bad = 4; The higher the score the worse the participant's speech is affecting his/her life	Baseline and 12 months
Change in Quality of Life as Measured by EORTC QLQ-C30	30 questions designed to assess the quality of life of cancer patients; The first 28 questions have answers that range from 1=not at all to 4 = very much. The higher score indicates a worse quality of life; The last 2 questions have answers that range from 1 = very poor to 7 = excellent. The higher score indicates a better quality of life	Baseline, 1 month, 6 months, 12 months, and 24 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Foundation for Barnes-Jewish Hospital
• Investigators: Principal Investigator: Jason Rich, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2013
• Primary Completion (Actual): October 18, 2019
• Study Completion (Actual): October 18, 2019

Study Registration Dates

• First Submitted: September 13, 2012
• First Submitted That Met QC Criteria: September 13, 2012
• First Posted (Estimate): September 18, 2012

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: 201207059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No