Clinical trial NCT05388773: Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Official title: Phase II Trial of Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oropharynx Cancer
Keywords: Papillomavirus Infections
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Papilloma
Neoplasms, Glandular and Epithelial
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
DNA Virus Infections
Tumor Virus Infections
Antineoplastic Agents
Intensity Modulated Radiotherapy
Carboplatin
Cisplatin
Transoral Surgery
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2022-05-24
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a trial studying patients with human papilloma virus (HPV) positive oropharyngeal cancer with tumors that can be removed via transoral surgery. Following surgery, patients will be classified as either low, intermediate, or high risk based on the characteristics of the tumors. Low risk patients (Arm S) will receive no further treatment after surgery. Intermediate risk patients (Arm RT) will be treated with Intensity Modulated Radiotherapy (IMRT) after surgery. High risk patients (Arm CRT) will receive a combination of IMRT and chemotherapy after surgery. Patients will be followed for up to five years after the completion of treatment.

Detailed description: This phase II trial is designed to rationally de-escalate adjuvant (Intensity Modulated Radiotherapy (IMRT) in the post-transoral surgery (TOS) setting in a study population consisting of patients with resectable oropharynx carcinoma, p16+ as confirmed by immunohistochemistry IHC, with a performance status (PS) of 0-1. Patients will be classified into one of three category/treatment groups (low-, intermediate-, and high-risk) according to their highest pathologically risk feature. Radiation will be given via an IMRT technique. For the high-risk patient group, a reduced, but slightly accelerated radiotherapy (RT) fractionation regimen of 50 Gy (HCC 18-034) in conjunction with cisplatin will be used compared to the standard 66 Gy and cisplatin. Low risk patients will transition to observation, intermediate risk patients will receive 30 Gy in 15 fractions of IMRT, and high risk patients will receive 50 Gy in 25 fractions (one day a week will include two treatments) plus 40 mg/m2 Cisplatin for 5 weeks. Patients who are not able to tolerate cisplatin will receive carboplatin instead.

Eligibility criteria: Inclusion Criteria:

* ECOG performance status of 0 or 1 or Karnofsky score 80-100.
* Newly diagnosed, histologically or cytologically confirmed SCC or undifferentiated carcinoma of the oropharynx and resectable oropharyngeal disease.
* Patients must be deemed eligible for a TOS procedure with no evidence of distant metastasis as determined by imaging studies.
* Biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node.
* Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a CLIA approved laboratory.
* No prior radiation above the clavicles.
* Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer.
* Patients with congestive heart failure \> NYHA Class II, CVA/TIA, unstable angina, or myocardial infarction within the last 6 months prior to registration must be evaluated by a cardiologist and/or neurologist.
* Acceptable renal and hepatic function within 4 weeks prior to registration as predefined.

Exclusion Criteria:

* No evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging.
* Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy.
* No intercurrent illness likely to interfere with protocol therapy or prevent surgical resection.
* No uncontrolled diabetes, infection despite antibiotics, or hypertension within 30 days prior to registration.

Primary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to 2 years (for cohort)
Secondary outcomes:
measure: Loco-regional control (at 1 year)
timeFrame: Up to 1 year
measure: Loco-regional control (at 2 years)
timeFrame: Up to 2 year
measure: Time to distant metastasis (at 1 year)
timeFrame: Up to 1 year
measure: Time to distant metastasis (at 2 years)
timeFrame: Up to 2 years
measure: Overall survival at 1 year
timeFrame: Up to 1 year
measure: Overall survival at 2 years
timeFrame: Up to 2 years
measure: Distribution of patients based on histologic risk features
timeFrame: Up to 3 years
measure: Assessment of PEG tube dependence
timeFrame: At 1 year (post treatment)
measure: Adverse Events Related to Treatment
timeFrame: Up to 5 years
measure: Quality of Life via FACT-HN
timeFrame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
measure: MD Anderson Symptom Inventory-Head & Neck (MDASI-HN)
timeFrame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, up to 2 years following treatment
measure: Modified Barium Swallow (MBS) rating
timeFrame: Before treatment, at 4-8 weeks post-surgery, 6 months and 24 months following treatment
measure: Voice outcomes
timeFrame: Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
measure: Performance Status Scale (PSS-HN)
timeFrame: Baseline (before treatment), at 4-8 weeks post-surgery, at 3 months, 6 months, 1 year, up to 2 years following treatment
measure: MD Anderson Dysphagia Inventory (MDADI)
timeFrame: Baseline (before treatment), at 4-8 weeks post-surgery, at 1 year, up to 2 years following treatment
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: UPMC Hillman Cancer Center
name: Heath Skinner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: