Human Papilloma VirusNCT02072148
The Sinai Robotic Surgery Trial in HPV Positive Oropharyngeal Squamous Cell Carcinoma (SCCA) (SIRS TRIAL)
A study testing PET/CT, Radiotherapy and Concurrent Chemoradiation in people with Human Papilloma Virus and Oropharyngeal Squamous Cell Carcinoma, run by Icahn School of Medicine at Mount Sinai at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Papilloma Virus, Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- PET/CT, Radiotherapy and Concurrent Chemoradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2014to 12 May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- 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
Who cannot join
- 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
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- 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.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mount Sinai Beth Israel
New York, New York, 10003
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: The Sinai Robotic Surgery Trial in HPV Positive Oropharyngeal Squamous Cell Carcinoma (SCCA)
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.
- Being tested
- PET/CT, Radiotherapy, Concurrent Chemoradiation
- Keywords
- Human Papilloma Virus, Oropharyngeal Squamous Cell Carcinoma, Transoral Robotic Surgery
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET/CTProcedure or surgery
PET scan or CT scan q 4 months for 5 years
RadiotherapyRadiation
Also called RT, XRT
Postoperative XRT 5000 cGy
Concurrent ChemoradiationRadiation
Also called CCRT, Cisplatin
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 ChemoradiationRadiation
Also called CCRT, Cisplatin
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
| Study group | Role | What they receive |
|---|---|---|
| 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, Receives: 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. Receives: Procedure: PET/CT; Radiation: Radiotherapy |
| High Risk Group IIIA | Experimental | * 3+ nodes, no ECS > 1mm
* Contralateral or supraclavicular nodes Receives: Procedure: PET/CT; Radiation: Concurrent Chemoradiation |
| High Risk Group IIIB | Experimental | * Incomplete surgical resection with + surgical margins
* ≥ 1 mm ECS
* Matted nodes Receives: Procedure: PET/CT; Radiation: Concurrent Chemoradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 5 years
Secondary outcomes (3)
Overall Survival
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.
Measured: 5 years
Number of Serious Adverse Events
Number of serious adverse events
Measured: 5 years
Global Quality of Life Scores
Global Quality of Life Scores total score from 0-100, with higher score indicating better health outcomes.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2014 (estimated)
- Study startMar 2014
- Primary completion12 May 2022
- Study completion12 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Human Papilloma VirusStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raymond Chai, Icahn School of Medicine at Mount Sinai
- Investigators
- Marshall Posner, MD, Study director, Icahn School of Medicine at Mount SinaiRaymond Chai, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02072148
- Sponsor's protocol ID
- GCO 13-1662
- Status last verified
- May 2024
- First submitted
- 24 Feb 2014
- Last updated
- 6 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Sinai Robotic Surgery Trial in HPV Positive Oropharyngeal Squamous Cell Carcinoma (SCCA)
- ClinicalTrials.gov ID
- NCT02072148
- Acronym / sponsor ID
- GCO 13-1662
- Keywords
- Human Papilloma Virus, Oropharyngeal Squamous Cell Carcinoma, Transoral Robotic Surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- 12 May 2022 (actual)
- Study completion
- 12 May 2022 (actual)
- First posted
- 26 Feb 2014 (estimated)
- Results
- Posted 6 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Risk Group I | Experimental | Procedure: PET/CTGroup 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 | Experimental | Procedure: PET/CT, Radiation: RadiotherapyGroup II * Complete resection (margins: tonsil <1mm, tongue <1mm, pT1-2, pN0-2B), * +LVI, +PNI, <3 positive nodes. ≤1mm ECS. |
| High Risk Group IIIA | Experimental | Procedure: PET/CT, Radiation: Concurrent Chemoradiation* 3+ nodes, no ECS > 1mm * Contralateral or supraclavicular nodes |
| High Risk Group IIIB | Experimental | Procedure: PET/CT, Radiation: Concurrent Chemoradiation* Incomplete surgical resection with + surgical margins * ≥ 1 mm ECS * Matted nodes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (17 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET/CTPET scan or CT scan q 4 months for 5 years | Procedure or surgery | High Risk Group IIIA, High Risk Group IIIB, Intermediate Risk Group II, Low Risk Group I |
| RadiotherapyAlso: RT, XRTPostoperative XRT 5000 cGy | Radiation | Intermediate Risk Group II |
| Concurrent ChemoradiationAlso: CCRT, CisplatinCCRT 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 | Radiation | High Risk Group IIIA |
| Concurrent ChemoradiationAlso: CCRT, CisplatinCCRT 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 | Radiation | High Risk Group IIIB |
Primary outcome
Disease Specific Survival (DSS)
Time frame: 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)
Time frame: 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)
Time frame: 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.
3 secondary outcomes
Overall Survival
Time frame: 5 years
Number of Serious Adverse Events
Time frame: 5 years
Global Quality of Life Scores
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marshall Posner, MD study director
Icahn School of Medicine at Mount Sinai
Raymond Chai, MD principal investigator
Icahn School of Medicine at Mount Sinai
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET/CT, Radiotherapy and Concurrent Chemoradiation in people with Human Papilloma Virus and Oropharyngeal Squamous Cell Carcinoma, run by Icahn School of Medicine at Mount Sinai at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Specific Survival (DSS) (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2024.