The Sinai Robotic Surgery Trial in HPV Positive Oropharyngeal Squamous Cell Carcinoma (SCCA) (SIRS TRIAL)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byRaymond Chai, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Icahn School of Medicine at Mount Sinai

No Placebo Group

Trial Summary

What is the purpose of this trial?

In general, patients with Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma (HPVOPC) are curable, young and will live for prolonged periods. They are at high risk for long-term toxicity and mortality from therapy. While the long-term consequences of chemotherapy and surgery for head and neck cancer are relatively constrained, high-dose radiotherapy (RT) and chemoradiotherapy (CRT) substantially impact on local tissues and organ function and result in a significant rate of late mortality and morbidity in patients. Studies are now being designed to reduce the impact of RT and CRT for patients. Patients with intermediate stage HPV positive oropharyngeal cancer will be screened for poor prognostic features and undergo robotic surgery. Patients in whom pathology demonstrates good prognosis features will then be followed without postoperative radiotherapy. Patients with subsequent recurrence will be treated with either surgery and postoperative radiotherapy or postoperative chemoradiotherapy alone. Patients with poor prognostic features (ECS, LVI, PNI) will receive reduced dose radiotherapy or chemoradiotherapy based on pathology. It is expected that over 50% of patients treated with surgery will have had a curative treatment and will avoid radiation therapy entirely and long-term survival will not be changed by withholding radiation therapy to good prognosis patients after surgery. There are exploratory biomarkers of risk of recurrence that will be collected and studied. There are currently few trials examining the role of de-escalation using surgery alone in intermediate and early T-stage HPV related disease. New surgical techniques have broadened the range of patients capable of achieving a complete resection and the functional outcomes in such patients are outstanding. Furthermore, the sensitivity of HPVOPC to chemotherapy and radiotherapy raise the possibility that delayed or salvage treatment in early stage patients would be highly effective, would result in similar survival outcomes and radiotherapy could be applied to a much smaller population then current standards call for. Looked at from a different perspective, the need for post-operative radiotherapy in this younger, HPV+ and more functional population has not been validated in clinical trials to date.

Research Team

Raymond Chai, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Marshall Posner, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Inclusion Criteria

Patients may be screened and consented if they display clinical features that are consistent with p16 positivity, they are p16+ but and not yet tested for p16 by IHC and for HPV by PCR and if they meet the other eligibility criteria. They will enter the experimental post-surgical portion of the study if they have surgery performed at MSSM and surgical specimens or biopsies proven to be both p16+ on IHC testing and HPV+ on PCR testing

Participants must have histologically or cytologically confirmed and identified resectable primary squamous cell carcinoma of the oropharynx that is HPV 16 positive or positive for any high risk HPV subtype (i.e., 18, 33, 35, etc.) as determined by PCR at the central laboratory. Patients must have p16+ status as determined by IHC performed or reviewed at the central laboratory prior to consent. Both p16 and HPV status must be determined prior to post-surgical adjuvant treatment assignment. Tissue from the primary site must be available for biomarker studies after surgery.

Stage 1, 2, 3 or early and intermediate stage IVa (T1N0-2B, T2N0-2B) (Level 2, non-matted) disease without evidence distant metastases or extracapsular extension. Primary site must be lateralized for a functional dissection.

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Treatment Details

Interventions

Concurrent Chemoradiation (Radiation)
Radiotherapy (Radiation)
Robotic Surgery (Surgery)

Participant Groups

4Treatment groups

Experimental Treatment

Group I: Low Risk Group IExperimental Treatment1 Intervention

Group I: * Complete resection (margins: tonsil \>1mm, tongue \>3mm, pT1-2, pN0-2B), * No LVI, no PNI, \<3 positive nodes. * No ECS, No matted or Level \>III,

Group II: Intermediate Risk Group IIExperimental Treatment2 Interventions

Group II * Complete resection (margins: tonsil \<1mm, tongue \<1mm, pT1-2, pN0-2B), * +LVI, +PNI, \<3 positive nodes. ≤1mm ECS.

Group III: High Risk Group IIIBExperimental Treatment2 Interventions

* Incomplete surgical resection with + surgical margins * ≥ 1 mm ECS * Matted nodes

Group IV: High Risk Group IIIAExperimental Treatment2 Interventions

* 3+ nodes, no ECS \> 1mm * Contralateral or supraclavicular nodes