Clinical trial NCT03144765: Multicenter Phase II Study of Transanal TME (taTME)
Official title: Multicenter Phase II Study of Transanal Total Mesorectal Excision (taTME) With Laparoscopic Assistance for Rectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Rectal Cancer
Surgery
Keywords: taTME
Transanal
Rectal cancer
Colorectal
Total mesorectal excision
TME
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Society of American Gastrointestinal and Endoscopic Surgeons
name: Research Foundation of the American Society of Colon and Rectal Surgeons
First posted: 2017-05-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Quality of Mesorectal Excision
timeFrame: 30 days
Secondary outcomes:
measure: Complete pathology assessment of TME specimens
timeFrame: 30 days
measure: 30-day perioperative complications
timeFrame: 30 days
measure: Long-term postoperative complications
timeFrame: 12 months
measure: Change in COREFO scores
timeFrame: 18 months
measure: Change in FIQLscores
timeFrame: 18 months
measure: Change in Wexner score
timeFrame: 18 months
measure: Change in International Index of Erectile Function [IIEF] score
timeFrame: 18 months
measure: Change in Female Sexual Function Index [FSFI]
timeFrame: 18 months
measure: Change in IPSS
timeFrame: 18 months
measure: 3-year oncologic outcomes
timeFrame: 3-5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Hospital
state: California
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Wynnewood
country: United States
facility: Lankenau Institute
state: Pennsylvania
city: Toronto
country: Canada
facility: Toronto Western Hospital
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Patricia Sylla, MD
role: PRINCIPAL_INVESTIGATOR
References: