Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer

NCT05388773 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: HCC 22-030
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Recurrence-Free Survival (RFS)

  Time to recurrence, defined as local and/or regional progression (identification of disease growth that is present within the area in which it was first located) and/or distant metastasis (identification of disease growth that is present in area(s) distant to that previously located). Local progression is defined as progression at the primary tumor site. Regional progression is defined as progression in the draining lymphatics (typically the cervical, retropharyngeal/retrostyloid and supraclavicular lymph nodes). Distant progression is defined as tumor recurrence in one or more non-local and non-regional sites (e.g., bone, lung, liver, etc.). Recurrent malignancy will be determined based on clinical exam and imaging findings. Patients who are disease-free but who die from other causes will be censored.

  Up to 2 years (for cohort)

Secondary Outcomes (15)

• Loco-regional control (at 1 year)

  Up to 1 year

• Loco-regional control (at 2 years)

  Up to 2 year

• Time to distant metastasis (at 1 year)

  Up to 1 year

• Time to distant metastasis (at 2 years)

  Up to 2 years

• Overall survival at 1 year

  Up to 1 year

Study Arms (3)

Arm S (Low Risk)

EXPERIMENTAL

Low risk patients are defined as T1-T2 AND 0 or 1 metastatic lymph nodes AND \<3 cm AND clear (≥3mm) margins AND no extracapsular extension (ECE) AND no perineural invasion AND no lymphovascular invasion. Patients will undergo transoral surgical resection of the oropharyngeal tumor.

Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: quality-of-life assessment

Arm RT (Intermediate Risk)

EXPERIMENTAL

Intermediate risk patients are defined as having any of the following features: One or more close (\<3mm) margins, OR "minimal" ≤1 mm ECE OR 1 or more metastatic lymph nodes \>3 cm in diameter OR 2-4 lymph nodes positive (≤ 6 cm in diameter), OR perineural invasion OR lymphovascular invasion Patients will undergo transoral surgical resection of the oropharyngeal tumor. Following surgery, patients will receive low-dose IMRT five times a week for 3 weeks.

Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: quality-of-life assessment; Radiation: intensity-modulated radiation therapy

Arm CRT (High Risk)

EXPERIMENTAL

High risk patients are defined as having any of the following features: One or more positive margins OR \>1 mm ECE OR ≥ 5 metastatic lymph nodes. Patients will undergo transoral surgical resection of the oropharyngeal tumor. Following surgery, patients will receive low-dose IMRT six times a week and a weekly chemotherapy infusion (cisplatin or carboplatin) during radiation therapy. Patients will receive 2 Gy/fraction, 6 fractions per week with at least a 6-hour interfraction interval between each treatment: * PTV-P50 or PTV-N50: 50 Gy in 25 fractions (2 Gy/fx) * PTV-N45: 45 Gy in 25 fractions (1.8 Gy/fx) with simultaneous integrated boost to the PTV-P50 volume. * PTV-P30 or PTV-N30: 30 Gy in 15 fractions (2 Gy/fx)

Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: quality-of-life assessment; Radiation: intensity-modulated radiation therapy; Drug: Cisplatin; Drug: Carboplatin

Interventions

therapeutic conventional surgery PROCEDURE

Transoral surgical resection of tumor(s).

Arm CRT (High Risk); Arm RT (Intermediate Risk); Arm S (Low Risk)

laboratory biomarker analysis OTHER

Correlative studies

Arm CRT (High Risk); Arm RT (Intermediate Risk); Arm S (Low Risk)

quality-of-life assessment OTHER

Ancillary studies.

Also known as: quality of life assessment

Arm CRT (High Risk); Arm RT (Intermediate Risk); Arm S (Low Risk)

intensity-modulated radiation therapy RADIATION

Low-dose IMRT

Also known as: IMRT

Arm CRT (High Risk); Arm RT (Intermediate Risk)

Cisplatin DRUG

Given IV.

Also known as: CACP, CDDP, CPDD, DDP

Arm CRT (High Risk)

Carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Arm CRT (High Risk)

Eligibility Criteria

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

You may qualify if:

• ECOG performance status of 0 or 1 or Karnofsky score 80-100.
• Preference is to register patients prior to surgery. However, if not registered prior to surgery, the patient can be registered prior to adjuvant therapy.
• Patients must have newly diagnosed, histologically or cytologically confirmed SCC or undifferentiated carcinoma of the oropharynx. Patients must have been determined to have resectable oropharyngeal disease. Patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible.
• Patients must be deemed eligible for a TOS procedure with no evidence of distant metastasis as determined by imaging studies. Metastatic disease may be evaluated using CT or PET/CT where appropriate; this can be performed with or without contrast. The following imaging is acceptable to evaluate the primary and regional disease:
• CT Neck (with contrast preferred but not required)
• PET/CT
• MRI Neck (contrast preferred but not required)
• Patients must have 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. It is required that patients have a positive p16 IHC (as surrogate for HPV) status from either 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. Using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended.
• 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 the following within the last 6 months prior to registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study.
• Congestive heart failure \> NYHA Class II
• CVA/TIA
• Unstable angina

You may not qualify if:

• No evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging.
• Patients must not need a microvascular (free flap) reconstruction. Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Patient must not have an intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
• Patients must not have uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within 30 days prior to registration.

Sponsors & Collaborators

• Heath Skinner: lead

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Papillomavirus Infections; Carcinoma, Squamous Cell; 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

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

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

Study Officials

• Heath Skinner, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brieana Marino, MS

CONTACT

412-647-8258; rowlesbm@upmc.edu

Samantha Demko, RN, BSN

CONTACT

412-623-1400; albesl@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: May 24, 2022
• Study Start: July 20, 2022
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)