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

NCT02072148 | Completed Results DMC

• 1 other identifier: GCO 13-1662
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 2

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.

Conditions

Human Papilloma Virus; Oropharyngeal Squamous Cell Carcinoma

Keywords

Human Papilloma Virus; Oropharyngeal Squamous Cell Carcinoma; Transoral Robotic Surgery

Outcome Measures

Primary Outcomes (3)

• Disease Specific Survival (DSS)

  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.

  5 years

• Number of Participants With Progression-Free Survival (PFS)

  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.

  5 years

• Number of Participants With Locoregional Failures (LRFs)

  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.

  5 years

Secondary Outcomes (3)

• Overall Survival

  5 years

• Number of Serious Adverse Events

  5 years

• Global Quality of Life Scores

  2 years

Study Arms (4)

Low Risk Group I

EXPERIMENTAL

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,

Procedure: PET/CT

Intermediate Risk Group II

EXPERIMENTAL

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

Procedure: PET/CT; Radiation: Radiotherapy

High Risk Group IIIA

EXPERIMENTAL

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

Procedure: PET/CT; Radiation: Concurrent Chemoradiation

High Risk Group IIIB

EXPERIMENTAL

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

Procedure: PET/CT; Radiation: Concurrent Chemoradiation

Interventions

PET/CT PROCEDURE

PET scan or CT scan q 4 months for 5 years

High Risk Group IIIA; High Risk Group IIIB; Intermediate Risk Group II; Low Risk Group I

Radiotherapy RADIATION

Postoperative XRT 5000 cGy

Also known as: RT, XRT

Intermediate Risk Group II

Concurrent Chemoradiation RADIATION

CCRT with cisplatin 40mg/m2/week IV over approximately 30 minutes, mixed in 250ml normal saline Weekly on Monday or Tuesday any time, or Wednesday prior to radiation Postoperative XRT 5000 cGy

Also known as: CCRT, Cisplatin

High Risk Group IIIA

Eligibility Criteria

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

You may qualify if:

• 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:
• Hematology:
• Neutrophil count \> 1.5 x 109/l.
• Platelet count \> 100 x 109/l.
• Hemoglobin \> 10 g/dl (may achieve by transfusion).
• Renal function: \> 60 ml/min (actual or calculated by the Cockcroft-Gault method) as follows:

You may not qualify if:

• 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:
• Unstable cardiac disease despite treatment, myocardial infarction with months prior to study entry.
• History of significant neurologic or psychiatric disorders including dementia or seizures
• Active clinically significant uncontrolled infection
• Active peptic ulcer disease defined as unhealed or clinically active
• Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis
• 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
• Autoimmune disease requiring therapy, prior organ transplant, or known HIV infection
• Interstitial lung disease
• Hepatitis C by history
• Concurrent treatment with any other anticancer therapy.
• Participation in an investigational therapeutic drug trial within 30 days of study entry.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (2)

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

Small sample size within each group limiting the generalizability of the reported results. The mean length of follow-up (43.8 months) is shorter than the standard 5-year reporting criteria.

Results Point of Contact

• Title: Dr. Raymond L Chai
• Organization: Icahn School of Medicine at Mount Sinai

Raymond.Chai@mountsinai.org

(212) 844-8775

Study Officials

• Marshall Posner, MD

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

• Raymond Chai, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Otolaryngology

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: February 26, 2014
• Study Start: March 1, 2014
• Primary Completion: May 12, 2022
• Study Completion: May 12, 2022
• Last Updated: May 6, 2024
• Results First Posted: May 6, 2024

Record last verified: 2024-05

Locations

US (2)