Clinical trial NCT01687413: Post Operative Adjuvant Therapy De-intensification Trial for Human Papillomavirus-related, p16+ Oropharynx Cancer
Official title: Adjuvant De-escalation, Extracapsular Spread, P16+, Transoral (ADEPT) Trial for Oropharynx Malignancy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Oropharyngeal Neoplasms
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: The Foundation for Barnes-Jewish Hospital
First posted: 2012-09-18
Enrollment: 42
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Disease-free Survival (DFS)
timeFrame: 1 year
measure: Locoregional Control
timeFrame: Up to 2 years
Secondary outcomes:
measure: Rate of Distant Metastasis
timeFrame: Up to 2 years
measure: Disease Specific Survival
timeFrame: 1 year
measure: Number of Complications/Acute Toxicity by Organ Class
timeFrame: Approximately 18 weeks
measure: Change in Quality of Life as Measured by the MD Anderson Dysphagia Inventory
timeFrame: Baseline, 1 month, 6 months, 12 months, and 24 months
measure: Change in Cognitive Function as Measured by Cognitive Failures Questionnaire
timeFrame: Baseline, 1 month, 12 months, and 24 months
measure: Change in Quality of Life as Measured by Neck Dissection Impairment Index (NDII)
timeFrame: Baseline, 12 months, and 24 months
measure: Change in Quality of Life as Measured by University of Michigan Xerostomia Questionnaire
timeFrame: Baseline, 1 month, 6 months, 12 months, and 24 months
measure: Change in Hearing as Measured by Hearing Handicap Inventory - Adult
timeFrame: Baseline, 1 month, and 12 months
measure: Change in Quality of Life as Measured by Scale of Subjective Total Taste Acuity
timeFrame: Baseline, 1 month, 6 months, and 12 months
measure: Change in Quality of Life as Measured by Speech Handicap Index
timeFrame: Baseline and 12 months
measure: Change in Quality of Life as Measured by EORTC QLQ-C30
timeFrame: Baseline, 1 month, 6 months, 12 months, and 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jason Rich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.