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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04066894

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

75.6

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This 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.

Condition or Disease	Intervention/Treatment	Phase
Fecal Incontinence 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 Adenocarcinoma Stage III Rectal Cancer AJCC v8 Stage IIIA Rectal Cancer AJCC v8 Stage IIIB Rectal Cancer AJCC v8 Stage IIIC Rectal Cancer AJCC v8 Stage IV Rectal Cancer AJCC v8 Stage IVA Rectal Cancer AJCC v8 Stage IVB Rectal Cancer AJCC v8 Stage IVC Rectal Cancer AJCC v8	Procedure: Explantation Other: Quality-of-Life Assessment Other: Questionnaire Administration Device: Sacral Nerve Stimulator Device: Sacral Nerve Stimulator Battery Procedure: Therapeutic Conventional Surgery	N/A

Detailed Description

PRIMARY OBJECTIVES:

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 and/or a restorative partial or complete proctectomy with colorectal or coloanal anastomosis for cancer treatment as per standard of care (restorative surgery cohort).
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:

To evaluate the effectiveness of sacral nerve stimulation (SNS) as measured by validated questionnaires in patients with FI or LARS within both patient cohorts.
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.
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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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)

Actual Study Start Date :

Apr 12, 2019

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Supportive Care (sacral nerve stimulator) 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.	Procedure: Explantation Undergo lead removal Other Names: Implant, removal of Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Device: Sacral Nerve Stimulator Undergo sacral nerve stimulator implantation Other Names: Sacral Neuromodulator Device: Sacral Nerve Stimulator Battery Undergo sacral nerve stimulator battery implantation Other Names: Sacral Neuromodulator Battery Procedure: Therapeutic Conventional Surgery Undergo sacral nerve stimulator implantation

Arm

Intervention/Treatment

Experimental: Supportive Care (sacral nerve stimulator)

Procedure: Explantation

Undergo lead removal

Other Names:

Implant, removal of

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Device: Sacral Nerve Stimulator

Undergo sacral nerve stimulator implantation

Other Names:

Sacral Neuromodulator

Device: Sacral Nerve Stimulator Battery

Undergo sacral nerve stimulator battery implantation

Other Names:

Sacral Neuromodulator Battery

Procedure: Therapeutic Conventional Surgery

Undergo sacral nerve stimulator implantation

Outcome Measures

Primary Outcome Measures

Proportion of patients with Sacral nerve stimulation (SNS) success [up to 2 weeks (+7) days post SNS placement]
Primary Outcome Measure should read only: "SNS success will be measured as a patient having the battery implanted up to 2 weeks (+7) days post SNS placement. Patients who do not have the SNS placed, for any reason other than insurance coverage issues, will count as not having a success."

Secondary Outcome Measures

Fecal Incontinence Severity Index [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. ranges from 0 to 61, a number of 30 has been shown to be reflective of severe fecal incontinence. the higher the severity of the fecal incontinence, no subscales
Fecal Incontinence Quality of Life Scale [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. Scales range from 1-5, scale scores are the averages responses to all questions divided by the number of items (29) on the scale Score of 1 indicates a lower functional status relating to quality of life Subscales: Lifestyle (10 items) Coping/Behavior (9 items) Depression/Self Perception (7 items) Embarrassment (3 items)
Anorectal manometry score [At 1 month after completion of surgery]
Will be reported descriptively with graphs or tabulations for anorectal manometry measures. The interpretation of the manometry findings will be documented but are not part of the determination as to if SNS is needed or not. They are not tabulated as part of a score. Anal Sphincter Electromyography: Surface Electrode Anal EMG is recording by placing small electrodes peri-anally.
Euroqol-5 Dimensions-5 Levels (EQ-5D-5L) [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) rated on 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems Additionally, participant is also asked to rate their health that day, from 0 to 100, 0 being the worst they could imagine, 100 being the best This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. Scores will be assessed and compared pre and post placement to reflect general quality of life
International Continence Society male Short Form [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. Higher scores indicate greater impact of individual symptoms on participant 11 items assessing Voiding (5) and Incontinence (6) - renders two scores Scoring: 0-20 voiding symptoms subscale 0-24 incontinence symptoms subscale Frequency, Nocturia and QoL scores indicate impact of symptoms for the patient separately Scale: Occasionally = less than one third of the time Sometimes = between one and two thirds of the time Most of the time = more than two thirds of the time
International Consultation on Incontinence Society - Female Lower Urinary Tract Symptoms [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. Overall score 0-48, (addition of all subscores) Higher scores indicate greater impact of individual symptoms on participant 12 items assessing Nocturia, Urgency, Bladder pain, Frequency, Hesitancy, Straining, Intermittency, Urge urinary incontinence, Frequency of urinary incontinence, Stress urinary incontinence, Unexplained urinary incontinence, Nocturnal enuresis Scoring: 0-16 filling symptoms subscale 0-12 voiding symptoms subscale 0-20 incontinence symptoms subscale Bother scales are not incorporated in the overall score but indicate impact of individual symptoms for the patient
Memorial Sloan Kettering Cancer Center Bowel Function Questionnaire (BFQ) (restorative surgery cohort) [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. five frequency options range from never to always (except for one question asking about the number of bowel movements per 24 hours) 18 questions (14 within subscales and with four single items do not belong to a subscale). A global score can be calculated as the sum of the subscale scores, and a total score can be calculated by adding all the item scores (subscale plus single item scores). A higher score represents better bowel function. Three subscales frequency, 6 items diet, 4 items urgency/soilage, 4 items
Low anterior resection syndrome score BFQ [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. range 0-42 points: ("no LARS": 0-20), ("minor LARS": 21-29), ("major LARS": 30-42). Major LARS requires treatment 5 issues graded, Incontinence for flatus (0: no, never; 4: yes, less than once/week; 7: yes, at least once/week) Incontinence for liquid stool (0: no, never; 3: yes, less than once/week; 3: yes, at least once/week) Frequency (4: >7x/day (24 hrs); 2: 4-7x/day, 0: 1-3x/day; 5: less than 1x/day) Clustering (0: no, never; 9: yes - less than once/week; 11: yes, at least once/week) Urgency (0: no, never; 11: yes - less than once/week; 16: yes, at least once/week)
Cleveland Clinic Incontinence Score (radiation cohort) [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. • 5 questions. The frequency with which each type of incontinence occurs is rated on a scale from 0 (never) to 4 (always or to 1/day). The sum of the frequencies is added for a total score that can range from 0 - 20, with higher scores indicating higher levels of incontinence.
Impact of SNS on bowel dysfunction [Up to 30 days (visit 2)]
Will be measured using bowel diaries.
Impact of SNS on urinary incontinence of the Bladder Diaries [Up to 30 days (visit 2)]
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 [Up to 3 years]
Will be reported descriptively with graphs or tabulations for categorical survey outcomes. has 5 functional and 18 symptom scales. Contains 4 subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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 with T1 and T2 pathologic stage patients treated with restorative surgical resection without radiation
Cohort 1: Patients with locally advanced rectal adenocarcinoma (T3 and T4 or lymph node positive) treated with radiation and restorative surgery
Cohort 1: Patients with self-reported FI or LARS
Cohort 1: Patients must 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 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
Cohort 2: Patients who are human immunodeficiency virus (HIV) positive (+) or have hepatitis B or C remain eligible, however, HIV+ patients must have a CD4 T cell count