Multicenter Phase II Study of Transanal TME (taTME)

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT03144765

Collaborator

Society of American Gastrointestinal and Endoscopic Surgeons (Other), Research Foundation of the American Society of Colon and Rectal Surgeons (Other)

100

Enrollment

Locations

Arm

91.4

Anticipated Duration (Months)

7.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Radical rectal cancer resection, namely total mesorectal excision (TME), is the cornerstone of the treatment of resectable rectal cancer. In combination with chemotherapy and radiation treatment (CRT), complete TME with negative resection margins is associated with sustained local and systemic control even in locally advanced disease. Over the last 2 decades, laparoscopic and robotic techniques have been increasingly adopted due to reduced surgical trauma and faster patient recovery. Yet, both approaches are associated with equivalent postoperative morbidity and disturbances in sexual, urinary and defecatory function relative to open TME. Furthermore, laparoscopic and robotic TME remain associated with substantial conversion rates and variable rates of TME completeness as a result of the procedural difficulties reaching the low rectum from the abdominal approach. Transanal TME (taTME) with laparoscopic assistance was developed to facilitate completion of TME using a primary transanal endoscopic approach. Transanal TME uses a "bottom-up approach" to overcome the technical difficulties of low pelvic dissection using an abdominal approach. Published results from single-center taTME series and an international registry suggest the short-term procedural and oncologic safety of this approach in resectable rectal cancer. No multicenter phase II study has yet been conducted to validate the procedural safety, functional outcomes or long-term oncologic outcomes of this approach.

Study Design: This is a 5-year phase II multicenter single-arm study to evaluate the safety and efficacy of low anterior resection (LAR) with taTME using laparoscopic or robotic assistance in 100 eligible subjects with resectable rectal cancer.

Hypothesis: taTME is non-inferior to standard LAR with respect to the quality of the TME achieved.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer Surgery	Procedure: Transanal Total Mesorectal Excision (taTME)	N/A

Detailed Description

The management of rectal cancer is multidisciplinary and outcomes are dependent on accurate preoperative staging, performance of a curative resection, and the selective use of neoadjuvant and adjuvant therapy to improve long-term oncologic outcomes. Despite the increasing use of laparoscopic and robotic approaches, radical rectal cancer resection is associated with relatively high rates of conversion to open surgery, variable rates of TME specimen completeness, and morbidity rates that are equivalent to that of open TME with respect to infectious and wound-related complications, as well as defecatory, sexual and urinary dysfunction,.

Transanal TME (taTME) with laparoscopic assistance was developed in an effort to facilitate completion of TME using a primarily transanal endoscopic approach. Based on the preliminary results from several published single-center case series and the first international taTME registry, in carefully selected patients with resectable rectal cancer, taTME with laparoscopic assistance is associated with perioperative outcomes and short-term oncologic outcomes that are equivalent to that of standard TME.

This study is the first phase II multicenter trial of taTME conducted in the United States to evaluate the efficacy and safety of taTME with laparoscopic or robotic assistance relative to standard LAR. A total of 100 subjects with resectable rectal cancer located up to 10 cm from the anal verge will be enrolled across 10 US study sites. It is anticipated that this larger, phase II multicenter study will validate the safety and efficacy of taTME with respect to perioperative outcomes, short and long-term oncologic outcomes and functional results.

Study procedure:

Study procedures will consist in 1-team (sequential) or 2-team (combined) LAR with transanal TME using laparoscopic or robotic abdominal assistance. Laparoscopic or robotic abdominal access will be obtained followed by inferior mesenteric vessels transection, mobilization or the proximal colon and splenic flexure takedown if indicated. Transanal TME is performed either at the same time or following the above steps. Intersphincteric resection (ISR) may be included for very low tumors. Following pursestring closure of the rectum below the tumor, transanal endoscopic TME dissection will proceed circumferentially until the peritoneal cavity is entered anteriorly. Following complete mobilization of the rectosigmoid, the specimen is extracted transanally or transabdominally followed by colorectal or coloanal anastomosis, with or without a diverting loop ileostomy. Operative details will be recorded in case report forms (CRF's).

TME pathology assessment:

Resected specimens will be processed and analyzed by the participating institution's Pathology Department according to standard TME protocol. De-identified photographs of all fresh TME specimens will be independently reviewed by a Pathology Review Committee blinded to the source of the specimen.

Postoperative care and follow-up:

Subjects will be managed according to standard postoperative protocols. Postoperative visits and oncology follow-up visits will occur as per standard practice and oncologic outcomes. All adverse events occurring during the study period will be graded using the Clavien-Dindo system. Postoperative functional questionnaires will be obtained 6-8 months and 12-14 months postoperatively in non-diverted subjects. In diverted subjects, functional questionnaires will be collected 3-4 months and 9-10 months following ileostomy closure (or 12-18 months following the study procedure).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter Phase II Study of Transanal Total Mesorectal Excision (taTME) With Laparoscopic Assistance for Rectal Cancer

Actual Study Start Date :

Apr 21, 2017

Anticipated Primary Completion Date :

May 30, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: taTME Enrolled subjects will undergo the study procedure, laparoscopically-assisted Transanal Total Mesorectal Excision (taTME).	Procedure: Transanal Total Mesorectal Excision (taTME) Study procedures consist in 1-team (sequential) or 2-team (combined) low anterior resection with transanal TME using laparoscopic or robotic abdominal assistance. Other Names: taTME

Arm

Intervention/Treatment

Experimental: taTME

Enrolled subjects will undergo the study procedure, laparoscopically-assisted Transanal Total Mesorectal Excision (taTME).

Procedure: Transanal Total Mesorectal Excision (taTME)

Study procedures consist in 1-team (sequential) or 2-team (combined) low anterior resection with transanal TME using laparoscopic or robotic abdominal assistance.

Other Names:

taTME

Outcome Measures

Primary Outcome Measures

Quality of Mesorectal Excision [30 days]
Rate of complete and near-complete mesorectal excision achieved with taTME, based on standard pathologic assessment of TME specimens.

Secondary Outcome Measures

Complete pathology assessment of TME specimens [30 days]
TNM grading, margins assessment
30-day perioperative complications [30 days]
The rate of complications experienced intraoperatively and postoperatively (within 30 days of the study procedure)
Long-term postoperative complications [12 months]
Incidence of long-term term postoperative complications
Change in COREFO scores [18 months]
Alterations in Colorectal Functional Outcome Questionnaire (COREFO) scores from baseline up to 18 months postoperatively - 27 items. All questions can be answered by choosing from five response options; No; Never; Yes, less than once a week; Yes, 1-2 days per week; Yes, 3-5 days per week; Yes, 6-7 days per week.
Change in FIQLscores [18 months]
Alterations in Fecal Incontinence Quality of Life Instrument (FIQL) scores from baseline up to 18 months postoperatively - 29 items range from 1 (strongly agree) to 4 (strongly disagree); with a 1 indicating a lower functional status of quality of life. Scale scores are only calculated if at least half of the items have been answered.
Change in Wexner score [18 months]
Alterations in Wexner score from baseline up to 18 months postoperatively. Wexner questionnaire - 5 questions and scored from 0 = never to 4= always, with total score from 0 (no incontinence) to 20 (complete incontinence)
Change in International Index of Erectile Function [IIEF] score [18 months]
Alterations in IIEF scores from baseline up to 18 months postoperatively - 15 item questionnaire, each item range from 0 - 5, with total score to 30. lower score indicates more severe erectile dysfunction (ED)
Change in Female Sexual Function Index [FSFI] [18 months]
Alterations in FSFI from baseline up to 18 months postoperatively - 19-item self-report measure, each item ranges from 0-5, with full range from 2 to 36, with low score indicating sexual function disorder.
Change in IPSS [18 months]
Alterations in International Prostate Symptom Score (IPSS) from baseline up to 18 months postoperatively - IPSS 8 questions total - 7 questions related to symptoms, each item scored 1-5. (asymptomatic to very symptomatic). The 8th question refers to the patient's perceived quality of life ranged from 0 to 6 ("delighted" to "terrible".) Total scale ranges from 8-35. Mild (symptom score less than of equal to 7), Moderate (symptom score range 8-19), Severe (symptom score range 20-35).
3-year oncologic outcomes [3-5 years]
3-year local recurrence rate, distant recurrence rate, disease-free survival and overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

New diagnosis of histologically confirmed adenocarcinoma of the rectum
Age ≥18
Clinical stage cT1 (high-risk), T2, or T3, cN0, N1, N2 on staging pelvic MRI
Negative predicted CRM on staging pelvic MRI
No evidence of metastasis on CT scans of the chest, abdomen and pelvis
Rectal cancer located within 10 cm from the anal verge based on proctoscopy and digital rectal examination (DRE)
Complete preoperative colonoscopy demonstrating no synchronous colon cancer
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Eligible to undergo laparoscopic or robotic LAR with or without a temporary diverting stoma, based on multidisciplinary tumor board consensus
Able to understand and willing to sign a written informed consent form

Exclusion Criteria:

cT4 on staging pelvic MRI
12 weeks delay between completion of neoadjuvant CRT and planned study procedure
Severely symptomatic rectal tumors
Tumors invading into the internal anal sphincter muscle based on DRE and pelvic MRI
Fecal incontinence at baseline
Prior history of rectal resection
Prior history of colorectal cancer
History of inflammatory bowel disease
Uncontrolled concurrent illness
Pregnancy
Subjects who cannot read or understand English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente	Los Angeles	California	United States	90027
2	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
3	UC Irvine Hospital	Orange	California	United States	92868
4	Florida Hospital	Orlando	Florida	United States	32804
5	Cleveland Clinic Florida	Weston	Florida	United States	33331
6	Lahey Clinic	Burlington	Massachusetts	United States	01805
7	University of Massachusetts	Worcester	Massachusetts	United States	01605
8	Mount Sinai Beth Israel	New York	New York	United States	10003
9	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
10	Cleveland Clinic	Cleveland	Ohio	United States	44195
11	Providence Portland Medical Center	Portland	Oregon	United States	97213
12	Lankenau Institute	Wynnewood	Pennsylvania	United States	19096
13	Toronto Western Hospital	Toronto		Canada