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

Primary Purpose

HPV-positive Oropharyngeal Squamous Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Robotic surgery
De-intensified XRT
Cisplatin
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV-positive Oropharyngeal Squamous Cell Carcinoma focused on measuring Oropharyngeal squamous cell carcinoma, OPSCC, Human papillomavirus, Transoral robotic surgery, TORS, HPV, p16, ctDNA, circulating tumor DNA, cfHPVDNA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • OPSCC with positive p16 immunohistochemistry and HR-HPV DNA or RNA PCR
  • Detectable baseline cfHPVDNA (greater than or equal to 10 fragments/mL)
  • Undetectable baseline cfHPVDNA (less than 5 fragments/mL)
  • Early and intermediate stage (T1N0-2B, T2N0-2B) disease without evidence of distant metastases or gross extranodal extension
  • Age > 18 years
  • No previous surgery, radiation therapy, or chemotherapy for head and neck cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Less than or equal to 20 pack year tobacco history with no active tobacco use
  • Adequate bone marrow, hepatic and renal functions
  • Undetectable cfHPVDNA after surgery. Undetectable cfHPVDNA is defined as <5 fragments/mL

Exclusion Criteria:

  • Advanced nodal stage (AJCC 7th edition N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, unequivocal radiographic extranodal extension, supraclavicular or matted metastatic disease, >3 radiographic pathologic cervical nodes
  • Previous or current malignancies at other locations, 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 by surgery and with no current evidence of disease for at least 5 years.
  • Non-high-risk HPV subtype on initial biopsy or final pathology
  • Presence of 5 or more positive nodes, irrespective of size, on final pathology
  • p16 negative or HPV negative OPSCC as determined by IHC and PCR or ISH, respectively.
  • Undetectable or < 5 copies/mL baseline cfHPVDNA prior to surgery
  • Detectable repeat cfHPVDNA 1-5 weeks postoperatively via the NavDX assay, defined as > 5 fragments/mL
  • Autoimmune disease treated with chemotherapy agents, anti TNF agents, or hydroxychloroquine within the last 5 years
  • Other serious illnesses or medical conditions
  • Participation in an investigational therapeutic drug trial within 30 days of study entry
  • Detectable repeat cfHPVDNA postoperatively, defined as >5 fragments/mL

Sites / Locations

  • Valley - Mount Sinai Comprehensive Cancer CareRecruiting
  • Mount Sinai Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Robotic surgery only

Robotic surgery with de-intensified adjuvant therapy

Arm Description

Complete resection to negative frozen section margins (pT1-2) < 4 nodes, ≤ 2 mm extranodal extension (ENE), no supraclavicular nodes

The presence of any of the following: 4 positive nodes, gross ENE, final positive margins, or bilateral neck disease High-risk PNI/LVI (defined as PNI and LVI in combination or either factor in the presence of 3 or more positive nodes)

Outcomes

Primary Outcome Measures

Local and/or regional disease recurrence (LRR)
Local and/or regional disease recurrence (LRR) at 2 years

Secondary Outcome Measures

Progression-free survival (PFS)
PFS at 2 years as defined as the proportion of patients without events (recurrence or death) at 2 years
Disease free survival (DFS)
PFS at 2 years as defined as the proportion of patients without events (recurrence or death) at 2 years
Overall Survival (OS)
OS at 2 years is defined as the proportion of patients alive at 2 years
M.D. Anderson Dysphagia Inventory
20 items instrument: a global assessment (a single question), it comprises three subscales: the emotional subscale (8 items), the functional subscale (5 items), and the physical subscale (6 items). The global assessment refers to the individual's swallowing difficulty as it affects one's overall daily routine. The emotional, functional, and physical subscales refer to the individual's affective response to the swallowing disorder, the impact of the disorder on daily activities, and the self-perception of the swallowing difficulties, respectively. Using a five-point scale (1-5), the minimum total score is 20 and the maximum 100. Higher score indicates the least interference with daily life.
Xerostomia Questionnaire (XQ)
Scale range from 1-10 (1 being dry as a desert and 10 is normal). Higher score indicates better health outcomes
European Organization of Research and Treatment Of Cancer (EORTC QLQ-C30)
EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. Scale ranges from 0-100. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.
European Organization of Research and Treatment of Head and Neck cancer questionnaire (EORTC QLQ-H&N35)
EORTC QLQ-H&N35 is a 35-question site-specific tool and is used in conjunction with EORTC QLQ-C30 measurement tool. Scale range from 0-100. Higher score indicates poorer health outcomes.
M.D. Anderson Symptom Inventory - Head & Neck (MDASI-HN)
MDASI-HN is a 28 symptom items questionnaire: 13 general cancer-related symptoms, such as pain, fatigue and nausea; 9 HNC-related symptoms, such as problems with mucus in the mouth and difficulty in swallowing or chewing; 6 items to evaluate the effects of symptoms on daily life, including mood and enjoyment of life. Each item is rated on a 11-point scale from 0 (not at all) to 10 (as bad as you can imagine), while the items that assess the interference of symptoms on daily activities are rated from 0 (does not interfere) to 10 (interfered completely). Subscales and full scale range from 0-10. Higher score indicates poorer health outcome.

Full Information

First Posted
June 10, 2022
Last Updated
May 11, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
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1. Study Identification

Unique Protocol Identification Number
NCT05419089
Brief Title
The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)
Official Title
The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2022 (Actual)
Primary Completion Date
June 2027 (Anticipated)
Study Completion Date
June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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), either with transoral robotic surgery (TORS) alone or combined with reduced doses of radiation and chemotherapy can result in cancer control and survival comparable to those previously reported with standard therapy. The hope is that with this newer approach, the long-term complications from chemotherapy and radiation can be reduced.
Detailed Description
There has been significant increase in the incidence of oropharynx cancer in North America and Europe. It is now understood that there are two dominant carcinogenic pathways for oropharyngeal squamous cell carcinoma. Environmentally related which is caused mainly by smoking and alcohol, and HPV-related oropharyngeal squamous cell carcinoma (HPVOPSCC). HPVOPSCC now accounts for over 80% of OPC seen in the USA and an increasing fraction of these malignancies in Europe. It has been shown that HPVOPSCC confers an excellent prognosis for intermediate staged disease and this has called into question the rational for aggressive concurrent chemoradiotherapy. High-dose radiotherapy (RT) and chemoradiotherapy (CRT) have substantial impact on local tissues and organ function and result in a significant rate of late mortality and morbidity. Studies are now being designed to reduce the impact of RT and CRT for patients. Recently, a new test has been developed that measures HPV circulating tumor DNA (cfHPVDNA) in the blood. The test has emerged as a promising biomarker for HPVOPSCC, correlating with both treatment response as well as surveillance for cancer recurrence. Data suggests that a negative test in the surveillance period following treatment is highly sensitive and specific for recurrent disease. In this trial, the study will be stratifying p16 positive patients with PCR detectable high-risk (HR) HPV DNA or RNA following TORS into risk groups based on final pathology to determine appropriate treatment intensity. Patients with low-risk pathologic disease and undetectable postoperative cfHPVDNA will receive no adjuvant therapy. Patients with high-risk pathologic disease and undetectable postoperative cfHPVDNA will receive de-intensified adjuvant radiation and chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV-positive Oropharyngeal Squamous Cell Carcinoma
Keywords
Oropharyngeal squamous cell carcinoma, OPSCC, Human papillomavirus, Transoral robotic surgery, TORS, HPV, p16, ctDNA, circulating tumor DNA, cfHPVDNA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Non-randomized non-inferiority
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
199 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Robotic surgery only
Arm Type
Experimental
Arm Description
Complete resection to negative frozen section margins (pT1-2) < 4 nodes, ≤ 2 mm extranodal extension (ENE), no supraclavicular nodes
Arm Title
Robotic surgery with de-intensified adjuvant therapy
Arm Type
Experimental
Arm Description
The presence of any of the following: 4 positive nodes, gross ENE, final positive margins, or bilateral neck disease High-risk PNI/LVI (defined as PNI and LVI in combination or either factor in the presence of 3 or more positive nodes)
Intervention Type
Procedure
Intervention Name(s)
Robotic surgery
Intervention Description
Transoral robotic surgical resection of the tumor with negative intraoperative frozen section margins.
Intervention Type
Radiation
Intervention Name(s)
De-intensified XRT
Intervention Description
Daily reduced-dose radiation treatment equal to 4600 cGy with either intensity-modulated radiotherapy (IMRT) or proton beam therapy
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Dose: 40mg/M2/week Route: IV over approximately 30 minutes, mixed in 250ml normal saline Schedule: Weekly on Monday or Tuesday any time, or Wednesday prior to radiation for 5 weeks (total dose 200 mg/M2)
Primary Outcome Measure Information:
Title
Local and/or regional disease recurrence (LRR)
Description
Local and/or regional disease recurrence (LRR) at 2 years
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
PFS at 2 years as defined as the proportion of patients without events (recurrence or death) at 2 years
Time Frame
2 years
Title
Disease free survival (DFS)
Description
PFS at 2 years as defined as the proportion of patients without events (recurrence or death) at 2 years
Time Frame
2 years
Title
Overall Survival (OS)
Description
OS at 2 years is defined as the proportion of patients alive at 2 years
Time Frame
2 years
Title
M.D. Anderson Dysphagia Inventory
Description
20 items instrument: a global assessment (a single question), it comprises three subscales: the emotional subscale (8 items), the functional subscale (5 items), and the physical subscale (6 items). The global assessment refers to the individual's swallowing difficulty as it affects one's overall daily routine. The emotional, functional, and physical subscales refer to the individual's affective response to the swallowing disorder, the impact of the disorder on daily activities, and the self-perception of the swallowing difficulties, respectively. Using a five-point scale (1-5), the minimum total score is 20 and the maximum 100. Higher score indicates the least interference with daily life.
Time Frame
2 years
Title
Xerostomia Questionnaire (XQ)
Description
Scale range from 1-10 (1 being dry as a desert and 10 is normal). Higher score indicates better health outcomes
Time Frame
2 years
Title
European Organization of Research and Treatment Of Cancer (EORTC QLQ-C30)
Description
EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. Scale ranges from 0-100. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.
Time Frame
2 years
Title
European Organization of Research and Treatment of Head and Neck cancer questionnaire (EORTC QLQ-H&N35)
Description
EORTC QLQ-H&N35 is a 35-question site-specific tool and is used in conjunction with EORTC QLQ-C30 measurement tool. Scale range from 0-100. Higher score indicates poorer health outcomes.
Time Frame
2 years
Title
M.D. Anderson Symptom Inventory - Head & Neck (MDASI-HN)
Description
MDASI-HN is a 28 symptom items questionnaire: 13 general cancer-related symptoms, such as pain, fatigue and nausea; 9 HNC-related symptoms, such as problems with mucus in the mouth and difficulty in swallowing or chewing; 6 items to evaluate the effects of symptoms on daily life, including mood and enjoyment of life. Each item is rated on a 11-point scale from 0 (not at all) to 10 (as bad as you can imagine), while the items that assess the interference of symptoms on daily activities are rated from 0 (does not interfere) to 10 (interfered completely). Subscales and full scale range from 0-10. Higher score indicates poorer health outcome.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: OPSCC with positive p16 immunohistochemistry and HR-HPV DNA or RNA PCR Detectable baseline cfHPVDNA (greater than or equal to 10 fragments/mL) Undetectable baseline cfHPVDNA (less than 5 fragments/mL) Early and intermediate stage (T1N0-2B, T2N0-2B) disease without evidence of distant metastases or gross extranodal extension Age > 18 years No previous surgery, radiation therapy, or chemotherapy for head and neck cancer Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Less than or equal to 20 pack year tobacco history with no active tobacco use Adequate bone marrow, hepatic and renal functions Undetectable cfHPVDNA after surgery. Undetectable cfHPVDNA is defined as <5 fragments/mL Exclusion Criteria: Advanced nodal stage (AJCC 7th edition N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, unequivocal radiographic extranodal extension, supraclavicular or matted metastatic disease, >3 radiographic pathologic cervical nodes 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. Non-high-risk HPV subtype on initial biopsy or final pathology Presence of 5 or more positive nodes, irrespective of size, on final pathology p16 negative or HPV negative OPSCC as determined by IHC and PCR or ISH, respectively. Undetectable or < 5 copies/mL baseline cfHPVDNA prior to surgery Detectable repeat cfHPVDNA 1-5 weeks postoperatively via the NavDX assay, defined as > 5 fragments/mL Autoimmune disease treated with chemotherapy agents or anti TNF agents within the last 2 years. Other serious illnesses or medical conditions Participation in an investigational therapeutic drug trial within 30 days of study entry Detectable repeat cfHPVDNA postoperatively, defined as >5 fragments/mL
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joshua Barlow
Phone
(212) 844-8775
Email
joshua.barlow@icahn.mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raymond Chai
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Valley - Mount Sinai Comprehensive Cancer Care
City
Paramus
State/Province
New Jersey
ZIP/Postal Code
07652
Country
United States
Individual Site Status
Recruiting
Facility Name
Mount Sinai Health System
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Barlow
Email
joshua.barlow@icahn.mssm.edu
First Name & Middle Initial & Last Name & Degree
Alecia Charles
Phone
(212) 241-7107
Email
Alecia.Charles@mountsinai.org
First Name & Middle Initial & Last Name & Degree
Raymond Chai, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification.
IPD Sharing Time Frame
Immediately following publication. No end date.

Learn more about this trial

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

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