Clinical trial NCT04370496: Safety of Minimally Invasive Surgery Using Endoscopic Stapler in Early Stage Cervical Cancer Patients (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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cervical Cancer
Cervical Cancer Stage IB1
Minimally Invasive Surgery
Keywords: Cervical cancer
Cervical Cancer Stage IB1
Minimally invasive surgery
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson
First posted: 2020-05-01
Enrollment: 124
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 4.5 year disease-free survival [DFS] rate
timeFrame: Examined at post-operative 4.5 years
Secondary outcomes:
measure: 4.5 year overall survival [OS] rate
timeFrame: Examined at post-operative 4.5 years
measure: Pattern of recurrence sites
timeFrame: 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
measure: Morbidity
timeFrame: Examined during operation and post-operative 4 and 6 weeks.
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Sungkyunkwan University School of Medicine
city: Suwon
country: Korea, Republic of
facility: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine
Study officials:
affiliation: Seoul National University Hospital
name: Hee Seung Kim, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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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 Aug 12.
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.
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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. doi: 10.1136/ijgc-2019-000388.
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-IIA2 cervical cancer. Gynecol Oncol. 2019 Apr;153(1):3-12. doi: 10.1016/j.ygyno.2019.01.008. Epub 2019 Jan 12.
citation: Park SJ, Kong TW, Kim T, Lee M, Choi CH, Shim SH, Yim GW, Lee S, Lee EJ, Lim MC, Chang SJ, Lee SJ, Lee SH, Song T, Lee YY, Kim HS, Nam EJ. Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol. BMC Cancer. 2022 Mar 26;22(1):331. doi: 10.1186/s12885-022-09429-z.
citation: Mun J, Park SJ, Yim GW, Chang SJ, Kim H; Trial Monitoring Committee of SOLUTION trial. Solution to prevent tumor spillage in minimally invasive radical hysterectomy using the endoscopic stapler for treating early-stage cervical cancer: Surgical technique with video. J Gynecol Obstet Hum Reprod. 2021 Dec;50(10):102211. doi: 10.1016/j.jogoh.2021.102211. Epub 2021 Sep 1.