Feasibility and Safety of Hybrid Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Colon Cancer

Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate the safety and efficacy of radical colectomy with hybrid transvaginal natural orifice transluminal endoscopic surgery (hvNOTES). This is a prospective, single-arm, multicenter, uncontrolled, open-label phase II study in 55 eligible subjects with resectable colon cancer. After informed consent, patients will be sent to have hvNOTES radical colectomy by surgeons with good experience in laparoscopic colorectal surgery. Patients' demographic, operative detail and postoperative outcomes including conversion to open surgery, operating time, blood loss, pain score, resumption of gastrointestinal function, postoperative complications, length of hospital stay, sexual function, quality of recovery, recurrence rate, recurrence patterns, relapse-free survival, and overall survival will be recorded prospectively. The results of the patients will be assessed to validate safety, functional outcomes or oncologic outcomes of hvNOTES colectomy.

Official Title
-----------------
A Phase II Study to Evaluate the Feasibility and Safety of Hybrid Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Treatment of Patients With Colon Cancer

Conditions
-----------------
Colon Cancer, Natural Orifice Transluminal Endoscopic Surgery

Intervention / Treatment
-----------------
* Procedure: hvNOTES radical colectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female. Age: over 18 and below 80 years old. BMI < 28 kg/m^2. American Society of Anesthesiologists score of class I to III. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Colonic adenocarcinoma by endoscopy with biopsy. Tumor size ≤ 5 cm. Involving a single colon segment: Right colon from the ileocecal valve up to and including the hepatic flexure. Left colon from the splenic flexure to the junction of the sigmoid and descending colon. Sigmoid colon between the descending colon and the rectum (at least 15 cm from the dentate). Clinical stage cT1, T2, or T3, cN0, N1, N2. No advanced local disease that renders laparoscopic resection impossible. No transverse colon cancer (between distal hepatic flexure and proximal splenic flexure). No distant metastasis in preoperative studies. Complete preoperative colonoscopy demonstrating no synchronous colon cancers. Require one of the following elective operations that may be safely performed by current techniques: Right hemicolectomy Left hemicolectomy Subtotal colectomy Sigmoid colectomy Patients who agree with participating in the clinical study with informed consents. And with willingness and ability to comply with the requirements of the study protocol including follow-up. Exclusion Criteria: Patients who have never experienced complete sexual intercourse before the operation. Previous intestinal surgery with any cause. cT4 tumor. Complications of colon cancer (bleeding, obstruction, or perforation). Previous neoadjuvant chemotherapy or radiotherapy for colon cancer. Patients who are diagnosed with other malignancies within 5 years. Vulnerable patients. Vaginal stenosis. Prior reconstructive surgery of the vagina not including hysterectomy. Unstable angina or myocardial infarction within the past 6 months. Cerebrovascular accident within the past 6 months. Continuous systemic steroid therapy within 1 month before the surgery. Patients who participating or participated in other clinical trial within 6 months. Pregnancy or breastfeeding. Any history of pelvic radiation. Anticipated need for an ostomy at the time of operation. Patients requiring urgent or emergent surgery. Patients with prior or suspected diagnosis of inflammatory bowel disease such as Crohn's disease, ulcerative colitis, or familial polyposis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hvNOTES group<br>Participants will undergo hvNOTES radical colectomy. | Procedure: hvNOTES radical colectomy<br>* With the patient under general anesthesia, pneumoperitoneum is achieved. Three trocars are inserted, one 12 mm or 5 mm in the umbilicus and two 5 mm in the right and/or left flanks. Mobilization of the splenic flexure or the hepatic flexure is performed with an initial traditional laparoscopic approach. A single-port is inserted into the abdominal cavity transvaginally through the colpotomy. Then most of the procedures are performed transvaginally with conventional rigid laparoscopic instruments. The corresponding arteries and veins are divided. The mesocolon is mobilized. The small intestine/colon/rectum are then divided with stapler. The specimen is removed transvaginally. Intracorporeal anastomosis is performed as per the surgeon's standard of care. For sigmoidectomy, the colon is then exteriorized and the anvil is fixed in the colon. An end-to-end anastomosis is performed using a circular stapler. Drainage tubes may be used.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications | The primary end point is major complication during surgery or within 90 days after surgery. A major intraoperative and postoperative complication is defined as a surgical or medical complication with a CTCAE grade of III or higher. The most severe complication in a patient was considered for the classification of the primary end point. | up to 90 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion to laparoscopic or open surgery | One of the secondary outcome measures is the rate of conversion to laparoscopic or open surgery as an indicator of surgical technical difficulty. Conversion is defined as the use of a laparoscopic port for the anastomosis, or a laparotomy wound for any part of the mesocolon dissection or the anastomosis. | during the surgery | 
| Concentration of c-reactive protein (CRP) | C-Reactive Protein (CRP) values on postoperative day 1and 3. | 1 and 3 postoperative days | 
| Concentration of procalcitonine (PCT) | Procalcitonine (PCT) values on postoperative day 1and 3. | 1 and 3 postoperative days | 
| Complete pathological assessment of CME specimens | Complete mesocolic excision (CME) is defined as complete resection of the mesocolon with its anatomical envelope. Rate of complete and near-CME achieved with hvNOTES, based on standard pathologic assessment of CME specimens. | up to 1 week after surgery | 
| Postoperative pain assessed by the numeric rating scale (NRS) | Pain score assessments: The investigator's staff will provide a rating scale to the patients to self-rate and record their pain at baseline (prior to surgery), at 24, 48, 72, 96, 120, 144, and 168 hours following the procedure end time (or discharge if earlier) postoperatively using the numeric rating scale (NRS) where 0 is for no pain and 10 is for the worst pain imaginable. | up to 1 week after surgery | 
| Amount of narcotic pain medication administered | The amount of narcotic pain medication administered through postoperative day 7 (or discharge if earlier) will be recorded (total dose of morphine equivalent during hospitalization and average dose per day). | up to 1 week after surgery | 
| Time to first flatus after surgery | Time to first flatus is defined as days from a colectomy procedure to first occurrence of flatus during subject's postoperative recovery. | up to 1 week after surgery | 
| Number of harvested lymph nodes | Number of harvested Lymph nodes according to the pathological report. | up to 1 week after surgery | 
| R0 resection | Rate of resection without any affected margins during the surgical procedure according to the pathological report. | up to 1 week after surgery | 
| Length of hospital stay | Days in the hospital after surgery. | up to 4 weeks after surgery | 
| Sexual function assessment | Patient self-reported sexual functions as assessed by the Female Sexual Function Index (FSFI). The FSFI is a 19-item questionnaire to rate sexual function between 2.0 and 36.0, where 2.0 is low sexual function and 36.0 is high sexual function. | baseline, 6 months, and 12 months after surgery | 
| Quality of recovery: Quality of Recovery 40 questionnaire (QoR-40) | Patient's quality of recovery is assessed by using the Quality of Recovery 40 questionnaire (QoR-40, score range: 40-200). Higher values represent better outcomes. The validate questionnaire measure quality of recovery by evaluating patients' comfort, emotions, physical independence, and support using the same scale. | 14 days after surgery | 
| Satisfaction with surgical scars: Validated questionnaire Patient Scar Assessment Questionnaire (PSAQ) | Validated questionnaire Patient Scar Assessment Questionnaire (PSAQ, score range: 28-102) will be administered to assess the patient's perception of scarring. Lower values represent better outcomes. The PSAQ consists of 5 subscales: Appearance, symptoms, consciousness, satisfaction with appearance, and satisfaction with symptoms. | 3, 6, and 12 months after surgery | 
| Quality of Life Questionnaire (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 | Quality of Life Questionnaire (QLQ) of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Score 3 months and 1 year after the procedure. This scale has functional, global health, and symptoms subscales/items all scored from 0 to 100. Higher scores on these subscales indicate high level of functioning, high quality of life, and high level of symptomatology, respectively. | baseline, 3 and 12 months after surgery | 
| Postoperative recurrence patterns | The recurrence patterns are determined according to the primary recurrence site diagnosed radiologically (CT, US, MRI, or PET-CT), or with histologic proof (ascitic cytology, colonoscopic biopsy, or surgery). | 2 years after surgery | 
| Relapse-free survival | Relapse-free survival is defined as the time from random assignment until disease relapse or death from any cause. | 2 years after surgery | 
| Overall survival | Overall survival is defined as time from surgery to death. | 2 years after surgery |