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

Not Applicable

Completed

Conditions: Oropharyngeal Squamous Cell Carcinoma
Human Papilloma Virus

Interventions: Procedure: PET/CT
Radiation: Concurrent Chemoradiation
Radiation: Radiotherapy

Registration Number: NCT02072148

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 112

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.
Age > 18 years.
No previous surgery, radiation therapy or chemotherapy for SCCHN (other than biopsy or tonsillectomy) is allowed at time of study entry.
ECOG performance status of 0 or 1.
No active alcohol addiction (as assessed by medical caregiver).
No active tobacco use (>10 years tobacco free interval, <20pk/yr. history)
Ability to understand and the willingness to sign a written informed consent document.
Participants must have adequate bone marrow, hepatic and renal functions as defined below:
1. Hematology:
  - Neutrophil count > 1.5 x 109/l.
  - Platelet count > 100 x 109/l.
  - Hemoglobin > 10 g/dl (may achieve by transfusion).
2. Renal function: > 60 ml/min (actual or calculated by the Cockcroft-Gault method) as follows:
  - CrCl (mL/min) = (140-age) (weight kg)
  - 72 x serum creatinine (mg/dL)
  - N.B. For females, use 85% of calculated CrCl value.
  - Or a Creatinine < the upper limits of normal

Exclusion Criteria

Patients < age 18.
Pregnant or breast feeding women.
Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, or other cancer curatively treated by surgery and with no current evidence of disease for at least 5 years.
Other serious illnesses or medical conditions including but not limited to:
1. Unstable cardiac disease despite treatment, myocardial infarction with months prior to study entry.
2. History of significant neurologic or psychiatric disorders including dementia or seizures
3. Active clinically significant uncontrolled infection
4. Active peptic ulcer disease defined as unhealed or clinically active
5. Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis
6. Chronic Obstructive Pulmonary Disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis. This does not include obstruction from tumor
7. Autoimmune disease requiring therapy, prior organ transplant, or known HIV infection
8. Interstitial lung disease
9. Hepatitis C by history
10. Concurrent treatment with any other anticancer therapy.
11. Participation in an investigational therapeutic drug trial within 30 days of study entry.
Advanced Stage III,IV (N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, obvious radiologic ECS, supraclavicular or matted metastatic disease, >3 cervical nodes. (These patients will be placed on the Quarterback trial due to advanced state of disease and poor prognostic features)
HPV negative OPSCC as determined by determined by PCR.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Risk Group I	PET/CT	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,
Intermediate Risk Group II	PET/CT	Group II * Complete resection (margins: tonsil \<1mm, tongue \<1mm, pT1-2, pN0-2B), * +LVI, +PNI, \<3 positive nodes. ≤1mm ECS.
High Risk Group IIIA	PET/CT	* 3+ nodes, no ECS \> 1mm * Contralateral or supraclavicular nodes
High Risk Group IIIB	Concurrent Chemoradiation	* Incomplete surgical resection with + surgical margins * ≥ 1 mm ECS * Matted nodes
High Risk Group IIIB	PET/CT	* Incomplete surgical resection with + surgical margins * ≥ 1 mm ECS * Matted nodes
Intermediate Risk Group II	Radiotherapy	Group II * Complete resection (margins: tonsil \<1mm, tongue \<1mm, pT1-2, pN0-2B), * +LVI, +PNI, \<3 positive nodes. ≤1mm ECS.
High Risk Group IIIA	Concurrent Chemoradiation	* 3+ nodes, no ECS \> 1mm * Contralateral or supraclavicular nodes

Primary Outcome Measures

Name	Time	Method
Disease Specific Survival (DSS)	5 years	Number of participants with HPV related oropharynx cancer treated with a de-intensified adjuvant protocol with status of disease specific survival. DSS was calculated by measuring the time from trial entry to cancer-related death.
Number of Participants With Progression-Free Survival (PFS)	5 years	Number of participants with HPV related oropharynx cancer treated with a de-intensified adjuvant protocol with status of progression-free survival. PFS calculated the time to biopsy confirmed recurrence or death from any cause.
Number of Participants With Locoregional Failures (LRFs)	5 years	the rate of local regional control (LRC) in patients with early and intermediate stage HPV related oropharynx cancer treated with surgery alone as assessed by number of participants with locoregional failures.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	5 years	Overall survival (OS) in patients with early and intermediate stage HPV related oropharynx cancer treated with surgery alone. OS from the time of entry to death with any cause.
Global Quality of Life Scores	2 years	Global Quality of Life Scores total score from 0-100, with higher score indicating better health outcomes.
Number of Serious Adverse Events	5 years	Number of serious adverse events

Trial Locations

Locations (2): Mount Sinai Beth Israel
🇺🇸
New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States