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

NCT01687413 | Terminated Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: 201207059
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

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.

Conditions

Oropharyngeal Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Rate of Distant Metastasis

  Up to 2 years

• Disease Specific Survival

  1 year

• Number of Complications/Acute Toxicity by Organ Class

  Approximately 18 weeks

• Change in Quality of Life as Measured by the MD Anderson Dysphagia Inventory

  Baseline, 1 month, 6 months, 12 months, and 24 months

• Change in Cognitive Function as Measured by Cognitive Failures Questionnaire

  Baseline, 1 month, 12 months, and 24 months

Study Arms (2)

Radiotherapy

EXPERIMENTAL

* 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)

Radiotherapy, cisplatin

ACTIVE COMPARATOR

* 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

Radiation: Intensity-modulated radiation therapy (IMRT); Drug: Cisplatin

Interventions

Intensity-modulated radiation therapy (IMRT) RADIATION

Radiotherapy; Radiotherapy, cisplatin

Cisplatin DRUG

Also known as: CACP, CDDP, CPDD, DDP, Neoplatin

Radiotherapy, cisplatin

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (2)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 25057165 DERIVED

Related Links

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

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Jason Rich, M.D.
• Organization: Washington University School of Medicine

richj@wustl.edu

314-747-3742

Study Officials

• Jason Rich, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 18, 2012
• Study Start: January 10, 2013
• Primary Completion: October 18, 2019
• Study Completion: October 18, 2019
• Last Updated: November 25, 2020
• Results First Posted: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)