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

Human Papilloma Virus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02072148
• Other study ID #: GCO 13-1662
• Status: Completed
• Phase: N/A
• Start date: March 2014
• Est. completion date: May 12, 2022

Study information

• Verified date: June 2022
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: May 12, 2022
• Est. primary completion date: May 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Human Papilloma Virus
• Oropharyngeal Squamous Cell Carcinoma
• Papilloma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Procedure:
• PET/CT
PET scan or CT scan q 4 months for 5 years

Radiation:
• Radiotherapy
Postoperative XRT 5000 cGy
• Concurrent Chemoradiation
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
• Concurrent Chemoradiation
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 5600 cGy

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai Beth Israel	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival	the rate of progression free survival (PFS) at 3 years in patients with HPV related oropharynx cancer treated with a de-intensified adjuvant protocol	3 years
Primary	Disease Free Survival	the rate of progression free survival (PFS) at 5 years in patients with early and intermediate stage HPV related oropharynx cancer treated with surgery alone	5 years
Primary	Local Regional Control	the rate of local regional control (LRC) at 3 years in patients with HPV related oropharynx cancer treated with a de-intensified adjuvant protocol	3 years
Primary	Local Regional Control	the rate of local regional control (LRC) at 5 years in patients with early and intermediate stage HPV related oropharynx cancer treated with surgery alone	5 years
Secondary	Overall Survival	overall survival (OS) at 3 years in patients with HPV related oropharynx cancer treated with a de-intensified adjuvant protocol	3 years
Secondary	Overall Survival	overall survival (OS) at 5 years in patients with early and intermediate stage HPV related oropharynx cancer treated with surgery alone	5 years
Secondary	Toxicity Rate	number of adverse events	3 years
Secondary	Toxicity Rate	number of adverse events	5 years
Secondary	Quality of Life Outcomes	Functional outcome data and quality of life - Scale comprised of: The European Organization for Research and Treatment of Cancer Core measure (EORTC QLQ-C30) is a well validated cancer-specific QOL scale that is used as a generic measurement for patients with cancer.; The M.D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) module is a validated instrument that provides a brief measure of the symptom distress experienced by the head and neck cancer patients as a result of their disease and/or treatment. This symptom burden instrument was closely associated with the severity of radiation-induced mucositis.; The MDA Xerostomia and Dysphagia questionnaires are radiotherapy/head and neck cancer directed questions which have a robust, validated assessment the specific concerns of swallowing and salivary function in head and neck cancer treated patients.	3 years
Secondary	Quality of Life Outcomes	Functional outcome data and quality of life	5 years
Secondary	Dose limiting Toxicity	Dose delays and dose modifications	up to 5 years