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

Cervical Cancer Clinical Trial

— SOLUTION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04370496
• Other study ID #: IRB No. 2002-101-1103
• Status: Recruiting
• Phase: N/A
• Start date: July 2, 2020
• Est. completion date: December 31, 2028

Study information

• Verified date: June 2023
• Source: Seoul National University Hospital
• Contact: Soo Jin Park, M.D.
• Phone: +82-02-2072-0897
• Email: soojin.mdpark[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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: 1. 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. 2. Insertions of uterine manipulators into the endometrial cavity is commonly done, which can cause tumor cells to travel to both salpinges. 3. Tumor cells can be exposed to the peritoneal cavity when the cervix is exposed during intracorporeal colpotomy. 4. 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. 1. The application of a vaginal tube instead of a uterine manipulator to prevent tumor cells from traveling to the salpinges. 2. The ligation of both salpinges prior to insertion of a vaginal tube to block the travel of tumor cells. 3. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Cervical Cancer Stage IB1
• Minimally Invasive Surgery
• Uterine Cervical Neoplasms

Intervention

Procedure:
• Minimally invasive surgery using endoscopic stapler
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.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center, Sungkyunkwan University School of Medicine	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine	Suwon

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Johnson & Johnson

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan 12;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X. — View Citation

Kim SI, Cho JH, Seol A, Kim YI, Lee M, Kim HS, Chung HH, Kim JW, Park NH, Song YS. Comparison of survival outcomes between minimally invasive surgery and conventional open surgery for radical hysterectomy as primary treatment in patients with stage IB1-II — View Citation

Kohler C, Hertel H, Herrmann J, Marnitz S, Mallmann P, Favero G, Plaikner A, Martus P, Gajda M, Schneider A. Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff - a multicenter analysis. Int J Gynecol Cancer. 2019 Jun;29(5):845-850 — View Citation

Nam JH, Park JY, Kim DY, Kim JH, Kim YM, Kim YT. Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study. Ann Oncol. 2012 Apr;23(4):903-11. doi: 10.1093/annonc/mdr360. Epub 2011 A — View Citation

Park JY, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. Laparoscopic versus open radical hysterectomy in patients with stage IB2 and IIA2 cervical cancer. J Surg Oncol. 2013 Jul;108(1):63-9. doi: 10.1002/jso.23347. Epub 2013 Jun 5. — View Citation

Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, Buda A, Yan X, Shuzhong Y, Chetty N, Isla D, Tamura M, Zhu T, Robledo KP, Gebski V, Asher R, Behan V, Nicklin JL, Coleman RL, Obermair A. Minimally Invasive versus Abdominal Radical Hysterec — View Citation

Wood DE. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Lung Cancer Screening. Thorac Surg Clin. 2015 May;25(2):185-97. doi: 10.1016/j.thorsurg.2014.12.003. Epub 2015 Jan 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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.