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Sacral Nerve Stimulation in Treating Low Anterior Resection Syndrome or Fecal Incontinence in Patients With Locally Advanced Rectal Cancer or Other Pelvic Cancer, the RESTORE Study

Primary Purpose

Low Anterior Resection Syndrome, Malignant Anal Neoplasm, Malignant Bladder Neoplasm

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Explantation
Quality-of-Life Assessment
Questionnaire Administration
Sacral Nerve Stimulator
Sacral Nerve Stimulator Battery
Therapeutic Conventional Surgery
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Low Anterior Resection Syndrome

Eligibility Criteria

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

Inclusion Criteria:

  • Cohort 1: Patients with pathologically proven diagnosis of primary rectal cancer
  • Cohort 1: Patients who have previously undergone surgical resection and anastomosis (restorative) with curative intent treatment with or without chemoradiation
  • Cohort 1: Patients treated with restorative surgical resection without radiation
  • Cohort 1: Patients with any T-stage or N-stage rectal cancer that underwent treatment with radiation and restorative surgery
  • Cohort 1: Patients with self-reported FI or LARS
  • Cohort 1: Patients must be at least 18 years old and be able to speak and understand English
  • Cohort 1: Patients must be willing to and able to sign an approved informed consent document
  • Cohort 1: Patients must be >= 24 months post-resection of rectal cancer
  • Cohort 1: Patients must have failed prior conservative measures such as Metamucil and motility medications and already been assessed and treated in a pelvic floor rehabilitation program (biofeedback) designed to treat FI and LARS, and continue to experience significant defecatory dysfunction, allowable per principal investigator (PI) discretion
  • Cohort 1: Patients must be willing and able to complete Patient Reported Outcomes Questionnaires for before device placement, during the testing phase following lead placement, and after implantation of the battery
  • Cohort 1: Patients must be willing and able to undergo elective ARM testing to objectively measure pelvic floor function
  • Cohort 1: Patients who have an average resting tone < 40 mmHg (normal > 40 mmHg) and maximal tolerance < 200 milliliters (normal 200-300 milliliters) as measured by ARM
  • Cohort 2: Patients with pathologically proven malignancy of the pelvis, other than rectal cancer (e.g. prostate, bladder, anus, vagina, vulva, cervix, uterus, or ovary)
  • Cohort 2: Patients treated with standard of care radiation therapies without surgical resection
  • Cohort 2: Patients with self-reported FI or other defecatory dysfunction
  • Cohort 2: Patients must be at least 18 years old and be able to speak and understand English
  • Cohort 2: Patients must be willing to and able to sign an approved informed consent document
  • Cohort 2: Patients must be >= 18 months post-pelvic chemoradiation
  • Cohort 2: Patients must have already been assessed and treated in a pelvic floor rehabilitation program design to treat FI or other defecatory dysfunction and continue to experience significant defecatory dysfunction
  • Cohort 2: Patients must be willing and able to complete Patient Reported Outcomes (PROs) and bowel and bladder diaries (Medtronic) at multiple times during the study
  • Cohort 2: Patients must be willing and able to undergo elective ARM testing to measure pelvic floor function
  • Cohort 2: Patients who have an average resting tone < 40 mmHg (normal > 40 mmHg) and maximal tolerance < 200 milliliters (normal 200-300 milliliters) as measured by ARM

Exclusion Criteria:

  • Cohort 1: Patients with co-morbid illnesses or concurrent disease, which in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Cohort 1: Any diverting bowel ostomy at the time of consent to this study
  • Cohort 1: Patients with an absolute neutrophil count (ANC) < 1.7 within 30 days of consent
  • Cohort 1: Patients with an international normalized rate (INR) > 1.3 within 30 days of consent
  • Cohort 1: Patients with a platelet count < 50 K within 30 days of consent
  • Cohort 1: Patients currently being treated with chemotherapy or within preceding 30 days at the time consent
  • Cohort 1: Patients previously treated with a SNS for urinary or FI
  • Cohort 1: Patients who were documented to have an anastomotic leak following their restorative surgical resection
  • Cohort 1: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status > 2 at the time of consent
  • Cohort 1: Patients with an active infection requiring systemic therapy at the time of consent
  • Cohort 1: Patients with a significant history of uncontrolled cardiac disease including, but not limited to hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failure
  • Cohort 2: Co-morbid illnesses or other concurrent disease, which in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Cohort 2: Patients with an ANC < 1.7 within 30 days of consent
  • Cohort 2: Patients with an INR > 1.3 within 30 days of consent
  • Cohort 2: Patients with a platelet count < 50 K, within 30 days of consent
  • Cohort 2: Patients currently being treated with chemotherapy or within the preceding 30 days at the time of consent
  • Cohort 2: Patients previously treated with a sacral nerve stimulator for urinary or fecal incontinence
  • Cohort 2: Patients with an ECOG performance status > 2 at the time of consent
  • Cohort 2: Patients with an active infection requiring systemic therapy at the time of consent
  • Cohort 2: Patients with a significant history of uncontrolled cardiac disease including, but not limited to hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failure
  • Cohort 2: Patients with an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study

Sites / Locations

  • M D Anderson Cancer Center
  • MD Anderson in Sugar Land

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive Care (sacral nerve stimulator)

Arm Description

Patients undergo scheduled, elective surgery for placement of the sacral nerve stimulator with external battery pack. After 2 weeks, patients undergo implantation of a subcutaneous internal battery or removal of the leads if the sacral nerve stimulator is working but does not improve symptoms. If the sacral nerve stimulator is not working, it is repositioned and patients return 2 weeks later for implantation of external battery or removal of leads.

Outcomes

Primary Outcome Measures

Sacral Nerve Stimulation (SNS) Success
SNS success will be measured as a patient having the battery implanted at visit 3. Patients who do not have the SNS placed, for any reason other than insurance coverage issues, will count as not having a success. Fecal incontinence will be measured by the physician as the total number of gas, mucus, liquid stool, and solid stool accidental leakage events reported in the bowel diaries. Improvement will be determined by the physician based on bowel diary comparisons recorded before SNS lead placement at visit 1 to after lead placement at visit 2. The proportion of patients who experience SNS success will be reported with a 90% credible interval using a beta (1,1)

Secondary Outcome Measures

Fecal Incontinence Severity Index Questionnaire Summary
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Fecal Incontinence Quality of Life Questionnaire Summary
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Euroqol-5 Dimensions-5 Levels (EQ-5D-5L)
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
International Consultation on Incontinence Society - Female Lower Urinary Tract Symptoms
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Memorial Sloan Kettering Cancer Center Bowel Function Questionnaire (BFQ)
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Low Anterior Resection Syndrome Score BFQ
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Cleveland Clinic Incontinence Score
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Impact of SNS on Bowel Dysfunction
Will be measured using bowel diaries.
Impact of SNS on Urinary Incontinence
Will be measured using bladder diaries and a post-void urinary bladder residual and validated urinary symptom questionnaire.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.

Full Information

First Posted
June 11, 2019
Last Updated
July 20, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04066894
Brief Title
Sacral Nerve Stimulation in Treating Low Anterior Resection Syndrome or Fecal Incontinence in Patients With Locally Advanced Rectal Cancer or Other Pelvic Cancer, the RESTORE Study
Official Title
A Phase II Study of Sacral Nerve Stimulation for Low Anterior Resection Syndrome or Fecal Incontinence in Patients Following a Low Anterior Resection or Proctectomy With Coloanal Anastomosis or in Patients After Pelvic Chemoradiation (RESTORE)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Due to Issues Enrolling Patients
Study Start Date
April 12, 2019 (Actual)
Primary Completion Date
September 1, 2022 (Actual)
Study Completion Date
September 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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

5. Study Description

Brief Summary
This phase II trial studies how well sacral nerve stimulation works in treating low anterior resection syndrome or fecal incontinence (the body's passage of stool without control) in patients with rectal cancer that has spread to nearby tissues or lymph nodes, or other pelvic cancer. Sacral nerve stimulation is a permanent implant that may improve bowel functions by stimulating the nerves that control the muscles related to bowel function.
Detailed Description
PRIMARY OBJECTIVES: I. To investigate the efficacy of sacral nerve stimulator placement in patients with fecal incontinence (FI) or low anterior resection syndrome (LARS) who have previously undergone chemoradiation treatment (XRT) and/or a restorative partial or complete proctectomy with colorectal or coloanal anastomosis for cancer treatment as per standard of care (restorative surgery cohort). II. To evaluate the feasibility of sacral nerve stimulator placement in patients with fecal incontinence (FI) or other defecatory dysfunction who have received pelvic radiation treatment without undergoing rectal or other pelvic surgery as per standard of cancer care (radiation only cohort). SECONDARY OBJECTIVES: I. To evaluate the effectiveness of sacral nerve stimulation (SNS) as measured by validated questionnaires in patients with FI or LARS within both patient cohorts. II. To evaluate pelvic floor and sphincter physiology using anorectal manometry (ARM) before and after SNS in patients with FI or LARS within both patient cohorts. III. To assess potential impact of SNS on urinary incontinence measuring a post-void urinary bladder residual and validated urinary symptom questionnaires in both patient cohorts. IV. To assess efficacy of SNS on long-term bowel dysfunction at 1 and 3 years post battery implantation as measured by validated questionnaires for both patient cohorts. OUTLINE: Patients undergo scheduled, elective surgery for placement of the sacral nerve stimulator with external battery pack. After 2 weeks, patients undergo implantation of a subcutaneous internal battery or removal of the leads if the sacral nerve stimulator is working but does not improve symptoms. If the sacral nerve stimulator is not working, it is repositioned and patients return 2 weeks later for implantation of external battery or removal of leads. After completion of study, patients are followed up at 1 month, 1 year, and 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Anterior Resection Syndrome, Malignant Anal Neoplasm, Malignant Bladder Neoplasm, Malignant Cervical Neoplasm, Malignant Ovarian Neoplasm, Malignant Pelvic Neoplasm, Malignant Prostate Neoplasm, Malignant Uterine Neoplasm, Malignant Vaginal Neoplasm, Malignant Vulvar Neoplasm, Rectal Carcinoma

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Supportive Care (sacral nerve stimulator)
Arm Type
Experimental
Arm Description
Patients undergo scheduled, elective surgery for placement of the sacral nerve stimulator with external battery pack. After 2 weeks, patients undergo implantation of a subcutaneous internal battery or removal of the leads if the sacral nerve stimulator is working but does not improve symptoms. If the sacral nerve stimulator is not working, it is repositioned and patients return 2 weeks later for implantation of external battery or removal of leads.
Intervention Type
Procedure
Intervention Name(s)
Explantation
Intervention Description
Undergo lead removal
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Device
Intervention Name(s)
Sacral Nerve Stimulator
Other Intervention Name(s)
Sacral Neuromodulator
Intervention Description
Undergo sacral nerve stimulator implantation
Intervention Type
Device
Intervention Name(s)
Sacral Nerve Stimulator Battery
Other Intervention Name(s)
Sacral Neuromodulator Battery
Intervention Description
Undergo sacral nerve stimulator battery implantation
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo sacral nerve stimulator implantation
Primary Outcome Measure Information:
Title
Sacral Nerve Stimulation (SNS) Success
Description
SNS success will be measured as a patient having the battery implanted at visit 3. Patients who do not have the SNS placed, for any reason other than insurance coverage issues, will count as not having a success. Fecal incontinence will be measured by the physician as the total number of gas, mucus, liquid stool, and solid stool accidental leakage events reported in the bowel diaries. Improvement will be determined by the physician based on bowel diary comparisons recorded before SNS lead placement at visit 1 to after lead placement at visit 2. The proportion of patients who experience SNS success will be reported with a 90% credible interval using a beta (1,1)
Time Frame
Up to visit 3
Secondary Outcome Measure Information:
Title
Fecal Incontinence Severity Index Questionnaire Summary
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Fecal Incontinence Quality of Life Questionnaire Summary
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Euroqol-5 Dimensions-5 Levels (EQ-5D-5L)
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
International Consultation on Incontinence Society - Female Lower Urinary Tract Symptoms
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Memorial Sloan Kettering Cancer Center Bowel Function Questionnaire (BFQ)
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Low Anterior Resection Syndrome Score BFQ
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Cleveland Clinic Incontinence Score
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years
Title
Impact of SNS on Bowel Dysfunction
Description
Will be measured using bowel diaries.
Time Frame
Up to 30 days (visit 2)
Title
Impact of SNS on Urinary Incontinence
Description
Will be measured using bladder diaries and a post-void urinary bladder residual and validated urinary symptom questionnaire.
Time Frame
Up to 30 days (visit 2)
Title
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29
Description
Will be reported descriptively with graphs or tabulations for categorical survey outcomes.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cohort 1: Patients with pathologically proven diagnosis of primary rectal cancer Cohort 1: Patients who have previously undergone surgical resection and anastomosis (restorative) with curative intent treatment with or without chemoradiation Cohort 1: Patients treated with restorative surgical resection without radiation Cohort 1: Patients with any T-stage or N-stage rectal cancer that underwent treatment with radiation and restorative surgery Cohort 1: Patients with self-reported FI or LARS Cohort 1: Patients must be at least 18 years old and be able to speak and understand English Cohort 1: Patients must be willing to and able to sign an approved informed consent document Cohort 1: Patients must be >= 24 months post-resection of rectal cancer Cohort 1: Patients must have failed prior conservative measures such as Metamucil and motility medications and already been assessed and treated in a pelvic floor rehabilitation program (biofeedback) designed to treat FI and LARS, and continue to experience significant defecatory dysfunction, allowable per principal investigator (PI) discretion Cohort 1: Patients must be willing and able to complete Patient Reported Outcomes Questionnaires for before device placement, during the testing phase following lead placement, and after implantation of the battery Cohort 1: Patients must be willing and able to undergo elective ARM testing to objectively measure pelvic floor function Cohort 1: Patients who have an average resting tone < 40 mmHg (normal > 40 mmHg) and maximal tolerance < 200 milliliters (normal 200-300 milliliters) as measured by ARM Cohort 2: Patients with pathologically proven malignancy of the pelvis, other than rectal cancer (e.g. prostate, bladder, anus, vagina, vulva, cervix, uterus, or ovary) Cohort 2: Patients treated with standard of care radiation therapies without surgical resection Cohort 2: Patients with self-reported FI or other defecatory dysfunction Cohort 2: Patients must be at least 18 years old and be able to speak and understand English Cohort 2: Patients must be willing to and able to sign an approved informed consent document Cohort 2: Patients must be >= 18 months post-pelvic chemoradiation Cohort 2: Patients must have already been assessed and treated in a pelvic floor rehabilitation program design to treat FI or other defecatory dysfunction and continue to experience significant defecatory dysfunction Cohort 2: Patients must be willing and able to complete Patient Reported Outcomes (PROs) and bowel and bladder diaries (Medtronic) at multiple times during the study Cohort 2: Patients must be willing and able to undergo elective ARM testing to measure pelvic floor function Cohort 2: Patients who have an average resting tone < 40 mmHg (normal > 40 mmHg) and maximal tolerance < 200 milliliters (normal 200-300 milliliters) as measured by ARM Exclusion Criteria: Cohort 1: Patients with co-morbid illnesses or concurrent disease, which in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Cohort 1: Any diverting bowel ostomy at the time of consent to this study Cohort 1: Patients with an absolute neutrophil count (ANC) < 1.7 within 30 days of consent Cohort 1: Patients with an international normalized rate (INR) > 1.3 within 30 days of consent Cohort 1: Patients with a platelet count < 50 K within 30 days of consent Cohort 1: Patients currently being treated with chemotherapy or within preceding 30 days at the time consent Cohort 1: Patients previously treated with a SNS for urinary or FI Cohort 1: Patients who were documented to have an anastomotic leak following their restorative surgical resection Cohort 1: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status > 2 at the time of consent Cohort 1: Patients with an active infection requiring systemic therapy at the time of consent Cohort 1: Patients with a significant history of uncontrolled cardiac disease including, but not limited to hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failure Cohort 2: Co-morbid illnesses or other concurrent disease, which in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Cohort 2: Patients with an ANC < 1.7 within 30 days of consent Cohort 2: Patients with an INR > 1.3 within 30 days of consent Cohort 2: Patients with a platelet count < 50 K, within 30 days of consent Cohort 2: Patients currently being treated with chemotherapy or within the preceding 30 days at the time of consent Cohort 2: Patients previously treated with a sacral nerve stimulator for urinary or fecal incontinence Cohort 2: Patients with an ECOG performance status > 2 at the time of consent Cohort 2: Patients with an active infection requiring systemic therapy at the time of consent Cohort 2: Patients with a significant history of uncontrolled cardiac disease including, but not limited to hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failure Cohort 2: Patients with an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A Messick, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
MD Anderson in Sugar Land
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center

Learn more about this trial

Sacral Nerve Stimulation in Treating Low Anterior Resection Syndrome or Fecal Incontinence in Patients With Locally Advanced Rectal Cancer or Other Pelvic Cancer, the RESTORE Study

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