Safety of Minimally Invasive Surgery Using Endoscopic Stapler in Early Stage Cervical Cancer Patients (SOLUTION)

Study Overview
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Brief Summary
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The SOLUTION trial aims to show the efficacy and safety of performing radical hysterectomy by minimally invasive surgery using an endoscopic stapler in patients with cervical cancer stage IB1 (FIGO staging 2009) and thus to prove that minimally invasive surgery is non-inferior to open surgery.

Detailed Description
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Cervical cancer is the 4th most common gynecologic cancer and treatment in early stages consists of surgery, chemotherapy, or radiation therapy. Surgical methods are simple or radical hysterectomy and pelvic and para-aortic lymph node dissection either done in an open manner or minimally invasive surgery (robotic or laparoscopic). However, a phase III cinical trial in 2018 comparing the safety and efficacy between minimally invasive surgery and open surgery in performing radical hysterectomy, 'Laparoscopic Approach to Cervical Cancer' (LACC), showed that open surgery is safer than minimally invasive surgery. Possible causes of such results are as follows: Carbon dioxide is supplied during laparoscopic operations to maintain capnoperitoneum, which can cause the implantation and proliferation of tumor cells exposed to the peritoneal cavity. Insertions of uterine manipulators into the endometrial cavity is commonly done, which can cause tumor cells to travel to both salpinges. Tumor cells can be exposed to the peritoneal cavity when the cervix is exposed during intracorporeal colpotomy. Tumor cells exposed to the peritoneal cavity can travel upwards when the patient's position is maintained in the Trendelenburg position during minimally invasive operations, leading to distant metastasis. Based on the above-mentioned hypothesis, the following methods could be applied to minimize the exposure of tumor cells to the peritoneal cavity. The application of a vaginal tube instead of a uterine manipulator to prevent tumor cells from traveling to the salpinges. The ligation of both salpinges prior to insertion of a vaginal tube to block the travel of tumor cells. The performance of extracorporeal colpotomy instead to prevent the exposure of tumor cells inside the peritoneal cavity. Although it would be favorable to perform all the forementioned methods, extracorporeal colpotomy is difficult to perform especially in menopausal patients with atrophic vaginitis or patients with no sexual experience. Thus, an alternative method is to use an endoscopic stapler which can simultaneously cut and suture the cervix into a vaginal stump, which can prevent tumor cells from being exposed to the peritoneal cavity. In conclusion, this clinical trial aims to show the efficacy and safety of performing radical hysterectomy by minimally invasive surgery using an endoscopic stapler in patients with cervical cancer stage IB1 (FIGO staging 2009) and thus to prove that minimally invasive surgery is non-inferior to open surgery.

Official Title
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Safety Of Laparoscopic or Robotic Radical Hysterectomy Using Endoscopic sTapler for Inhibiting tumOr Spillage of Cervical Neoplasms (SOLUTION): a Phase II Study

Conditions
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Cervical Cancer, Cervical Cancer Stage IB1, Minimally Invasive Surgery

Intervention / Treatment
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* Procedure: Minimally invasive surgery using endoscopic stapler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females, aged 20 years or older Histologically confirmed primary squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the uterine cervix Patients with FIGO stage IB1 (FIGO staging 2009) : stromal invasion>5 mm or 7 mm <lesion size ≤4 cm Patients undergoing either type B or C hysterectomy (Querleu-Morrow classification) Patients with normal bone marrow, renal and hepatic function WBC > 3.0x10^9 cells/L Platelets > 100x10^9 cells/L Serum creatinine ≤1.5 mg/dL Serum total bilirubin <1.5 x normal range and AST/SGOT or ALT/SGPT <3 x normal range ECOG performance status 0 or 1 Synchronous cancer with no evidence of recurrence during the past 5 years Informed consent of patient Exclusion Criteria: Any histological type other than squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the uterine cervix Tumor size greater than 4 cm Patients with FIGO less than stage IA2 or greater than IB2 (FIGO staging 2009) stromal invasion ≤5 mm and lesion size ≤7 mm (less than IA2) or lesion size> 4 cm (greater than IB2) Patients with evidence of metastatic disease by conventional imaging studies, enlarged pelvic or aortic lymph nodes greater than 2 cm, or histologically positive lymph nodes Patients in pregnancy Patients with a history of pelvic or abdominal radiotherapy Patients with contraindication of surgery (serious concomitant systemic disorders incompatible with the study to be decided at the discretion of the investigator) Patients who agree to intra-operative lymphatic mapping (IOLM) must not have: Known allergies to triphenylmethane compounds History of retroperitoneal surgery. History of pelvic irradiation. Cold knife or LEEP cone biopsy within 4 weeks of enrollment

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients enrolled in this clinical trial will undergo surgery for early stage cervical cancer. They will receive either laparoscopic or robotic radical hysterectomy using an endoscopic stapler. The efficacy and safety of this surgical technique will be compared to that of open radical hysterectomy studied in previous trials.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOLUTION group<br>Patients enrolled in this clinical trial will undergo radical hysterectomy through minimally invasive surgery using an endoscopic stapler which both cuts and simultaneously sutures the open vaginal stump. | Procedure: Minimally invasive surgery using endoscopic stapler<br>* Radical hysterectomy by minimally invasive surgery (laparoscopic or robotic) will be done with the help of an endoscopic stapler in cutting and suturing the uterine cervix.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4.5 year disease-free survival [DFS] rate | Probability of no recurrence from the day of surgery until post-operative 4.5 years | Examined at post-operative 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4.5 year overall survival [OS] rate | Rate of survival from the day of surgery until post-operative 4.5 years | Examined at post-operative 4.5 years | 
| Pattern of recurrence sites | Anatomical site of recurrent cancer according to imaging modalities | Examined every 3 months during post-operative 1 year, every 2 months during post-operative 2 years, and every 6 months during post-operative 4.5 years | 
| Morbidity | Intra-operative and post-operative complications occurring in less than post-operative 4 weeks and between post-operative 4 and 6 weeks. Other morbidity include estimated blood loss during surgery, post-operative pain and amount of analgesic consumption | Examined during operation and post-operative 4 and 6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical cancer, Cervical Cancer Stage IB1, Minimally invasive surgery