RECRUITING

The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)

Conditions

HPV-positive Oropharyngeal Squamous Cell Carcinoma Oropharyngeal squamous cell carcinoma OPSCC Human papillomavirus Transoral robotic surgery TORS HPV p16 ctDNA circulating tumor DNA cfHPVDNA

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to determine whether treatment of HPV-related oropharyngeal squamous cell carcinoma in patients with undetectable postoperative HPV circulating tumor DNA (cfHPVDNA) with transoral robotic surgery (TORS) alone can result in cancer control and survival comparable to those previously reported with standard therapy. The protocol includes patients with only with low or intermediate pathologic risk factors following surgery with detectable pre-surgery cfHPVDNA and undetectable post-surgery cfHPVDNA. The hope is that with this approach, the long-term complications from chemotherapy and radiation can be reduced.

Official Title

The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)

Quick Facts

Study Start:2022-07-12

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05419089

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must have histologically or cytologically confirmed and identified resectable primary OPSCC with positive p16 immunohistochemistry, defined as strong and diffuse nuclear and cytoplasmic staining in \> 70% of tumor cells. Immunohistochemistry must be performed or reviewed at the central laboratory. P16 status may be determined prior to consent and must be confirmed by surgical specimen if a biopsy is unavailable. HR-HPV status and postoperative cfHPVDNA testing must be performed and resulted prior to treatment assignment. Tissue from the primary site must be available for biomarker studies after surgery. * Patients enrolled in the trial must have pre-surgery baseline cfHPVDNA using the NavDX assay (Naveris, Cambridge, MA). Detectable baseline cfHPVDNA copy number is defined as ≥ 10 fragments/mL and is required for inclusion in the trial. * Undetectable cfHPVDNA after surgery. All patients should have a repeat cfHPVDNA test within 1 to 5 weeks post-operatively and prior to treatment assignment. Undetectable cfHPVDNA is defined as \< 5 fragments/mL. * AJCC 7th edition early and intermediate stage (T1N0-2B, T2N0-2B) (non-matted) disease without evidence of distant metastases or gross extranodal extension. * Age ≥ 18 years at screening * No previous surgery, radiation therapy, or chemotherapy for head and neck cancer (other than excision/incisional biopsy of the primary site, excisional/incisional nodal biopsy, or tonsillectomy) is allowed at time of study entry. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * No active tobacco use (≥1cigarette or cigarette-equivalent per day within the last 5 years) and no cumulative smoking history of \>20 pack years. 1 cigar = 4 cigarette-equivalent exposure * 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: * Platelet count ≥ 90 x 109/l. * Hemoglobin ≥ 10 g/dl (may achieve by transfusion). * Renal function: eGFR ≥ 50 ml/min * Age \< 18 years at screening * Pregnant or breast-feeding women. * Previous or current malignancies at other sites, except for adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, prostate cancer treated with surgery/radiotherapy, ductal carcinoma in situ of the breast treated with surgery/radiotherapy, or other cancer curatively treated and with no current evidence of disease for at least 3 years. * Other serious illnesses or medical conditions including but not limited to: * Unstable cardiac disease despite treatment or myocardial infarction within 6 months prior to study entry. * History of significant neurologic or psychiatric disorders including severe dementia or poorly controlled 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 * Severe chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia within 12 months of diagnosis. * Prior organ transplant * Interstitial lung disease * Concurrent treatment with any other anti-cancer therapy * Participation in an investigational therapeutic drug trial within 30 days of study entry. Participation in additional investigational radiation studies will exclude participation in SIRS. Participation in non-therapeutic, non-oncologic investigational studies (i.e. pain control studies, nutritional studies, etc.) will be allowed amongst SIRS participants, provided there is no alteration of treatment planning, oncologic therapy, or surveillance, and additional studies comply with SIRS safety criteria and stopping rules as outlined in the SIRS protocol. * Active hepatitis C by history * Advanced nodal stage (AJCC 7th edition N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, unequivocal radiographic extranodal extension, unequivocal radiographic or clinical supraclavicular or matted metastatic disease, \> 3 unequivocally radiographic pathologic cervical nodes. * Non-HR-HPV subtype on initial biopsy or final pathology. * 5 or more positive nodes, irrespective of size, on final pathology. * p16 or HPV negative OPSCC as determined by IHC and PCR or ISH, respectively. * Undetectable or \< 10 fragments/mL baseline cfHPVDNA prior to surgery. * Autoimmune disease treated with chemotherapy agents or anti TNF agents within the last 2 years. * Detectable repeat cfHPVDNA 1-5 weeks postoperatively via the NavDX assay, defined as \> 5 fragments/mL.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* Patients must have histologically or cytologically confirmed and identified resectable primary OPSCC with positive p16 immunohistochemistry, defined as strong and diffuse nuclear and cytoplasmic staining in \> 70% of tumor cells. Immunohistochemistry must be performed or reviewed at the central laboratory. P16 status may be determined prior to consent and must be confirmed by surgical specimen if a biopsy is unavailable. HR-HPV status and postoperative cfHPVDNA testing must be performed and resulted prior to treatment assignment. Tissue from the primary site must be available for biomarker studies after surgery.
* Patients enrolled in the trial must have pre-surgery baseline cfHPVDNA using the NavDX assay (Naveris, Cambridge, MA). Detectable baseline cfHPVDNA copy number is defined as ≥ 10 fragments/mL and is required for inclusion in the trial.
* Undetectable cfHPVDNA after surgery. All patients should have a repeat cfHPVDNA test within 1 to 5 weeks post-operatively and prior to treatment assignment. Undetectable cfHPVDNA is defined as \< 5 fragments/mL.
* AJCC 7th edition early and intermediate stage (T1N0-2B, T2N0-2B) (non-matted) disease without evidence of distant metastases or gross extranodal extension.
* Age ≥ 18 years at screening
* No previous surgery, radiation therapy, or chemotherapy for head and neck cancer (other than excision/incisional biopsy of the primary site, excisional/incisional nodal biopsy, or tonsillectomy) is allowed at time of study entry.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* No active tobacco use (≥1cigarette or cigarette-equivalent per day within the last 5 years) and no cumulative smoking history of \>20 pack years. 1 cigar = 4 cigarette-equivalent exposure
* 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:
* Platelet count ≥ 90 x 109/l.
* Hemoglobin ≥ 10 g/dl (may achieve by transfusion).
* Renal function: eGFR ≥ 50 ml/min
* Age \< 18 years at screening
* Pregnant or breast-feeding women.
* Previous or current malignancies at other sites, except for adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, prostate cancer treated with surgery/radiotherapy, ductal carcinoma in situ of the breast treated with surgery/radiotherapy, or other cancer curatively treated and with no current evidence of disease for at least 3 years.
* Other serious illnesses or medical conditions including but not limited to:
* Unstable cardiac disease despite treatment or myocardial infarction within 6 months prior to study entry.
* History of significant neurologic or psychiatric disorders including severe dementia or poorly controlled 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
* Severe chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia within 12 months of diagnosis.
* Prior organ transplant
* Interstitial lung disease
* Concurrent treatment with any other anti-cancer therapy
* Participation in an investigational therapeutic drug trial within 30 days of study entry. Participation in additional investigational radiation studies will exclude participation in SIRS. Participation in non-therapeutic, non-oncologic investigational studies (i.e. pain control studies, nutritional studies, etc.) will be allowed amongst SIRS participants, provided there is no alteration of treatment planning, oncologic therapy, or surveillance, and additional studies comply with SIRS safety criteria and stopping rules as outlined in the SIRS protocol.
* Active hepatitis C by history
* Advanced nodal stage (AJCC 7th edition N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, unequivocal radiographic extranodal extension, unequivocal radiographic or clinical supraclavicular or matted metastatic disease, \> 3 unequivocally radiographic pathologic cervical nodes.
* Non-HR-HPV subtype on initial biopsy or final pathology.
* 5 or more positive nodes, irrespective of size, on final pathology.
* p16 or HPV negative OPSCC as determined by IHC and PCR or ISH, respectively.
* Undetectable or \< 10 fragments/mL baseline cfHPVDNA prior to surgery.
* Autoimmune disease treated with chemotherapy agents or anti TNF agents within the last 2 years.
* Detectable repeat cfHPVDNA 1-5 weeks postoperatively via the NavDX assay, defined as \> 5 fragments/mL.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Tanvir Queraishi

CONTACT

(908) 340-7842

tanvir.queraishi@mountsinai.org

Principal Investigator

Raymond Chai

PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Study Locations (Sites)

Valley - Mount Sinai Comprehensive Cancer Care

Paramus, New Jersey, 07652

United States

Mount Sinai Health System

New York, New York, 10019

United States

Collaborators and Investigators

Sponsor: Icahn School of Medicine at Mount Sinai

Raymond Chai, PRINCIPAL_INVESTIGATOR, Icahn School of Medicine at Mount Sinai

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-12

Study Completion Date2027-06

Study Record Updates

Study Start Date2022-07-12

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

Oropharyngeal squamous cell carcinoma
OPSCC
Human papillomavirus
Transoral robotic surgery
TORS
HPV
p16
ctDNA
circulating tumor DNA
cfHPVDNA

Additional Relevant MeSH Terms

HPV-positive Oropharyngeal Squamous Cell Carcinoma