A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer

Official title

A Randomized Controlled Trial of Robotic Versus Open Surgery for Early Stage Cervical Cancer (ROCC)

Overview

This is a randomized controlled trial to compare survival for patients who undergoe robotic assisted laparoscopy versus open hysterectomy and lymph node assessment for the treatment of early stage cervical cancer.

Detailed description

This is a multi-center, open-label, randomized, non-inferiority clinical trial with the hypothesis that robotically assisted hysterectomy with tumor containment prior to colpotomy is non-inferior to abdominal hysterectomy with respect to disease free survival.

At the commencement of surgery, a thorough inspection of all peritoneal surfaces should be performed. The location of any suspected metastatic disease should be documented in the operative report and a biopsy should be performed to confirm the diagnosis. If intraperitoneal disease is detected, the radical hysterectomy should be abandoned. In patients with macroscopic evidence of metastatic disease to the lymph nodes, intraoperative frozen section should be performed to confirm the presence of metastatic disease. Intraoperative management will be left to the discretion of the surgeon. Patients who have confirmed macroscopic lymph node metastases intraoperatively will be excluded from final analysis and replaced due to the controversy surrounding the decision to perform a radical hysterectomy in this setting. Patients in whom the hysterectomy is abandoned will be deemed non-evaluable and excluded from final analysis and will be replaced. For all patients, the surgeon should document operative time from incision to close, detailed description of operative findings, intraoperative complications, and blood loss. For patients randomized to the robotic arm, the surgeon should document the use of and specify the type of vaginal manipulator and the reason for conversion to laparotomy (if applicable). Transcervical manipulators are not permitted.

Standard arm: Radical or simple hysterectomy is performed as per standard technique (peon radical hysterectomy (Piver type 2 or 3 or Querleu \& Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. Prior to colpotomy, the vagina must be closed over the tumor (ie, Wertheim clamps, contour stapling device).

Study arm: Radical or simple hysterectomy is performed as per standard robotic technique (Querleu \& Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. Colpotomy may be made intracorporally or vaginally. Vagina must be closed prior to intracorporeal colpotomy (see below, #10)

Interventions

• Device da Vinci
  Minimally invasive robotic-assisted radical or simple hysterectomy
• Other open surgery
  open radical or simple hysterectomy

Primary outcome measures

• Survival [Time frame: 36 months]

Eligibility criteria

Inclusion criteria

• Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS), squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
• Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive parametrial, vaginal, nodal or distant metastases on exam or imaging. Patients with tumor size less than or equal to 4 cm confirmed on MRI prior to randomization are eligible.
• Patient must have uterine size <12 cm AND felt to be appropriate for vaginal delivery of the specimen per investigator.
• Patient must be suitable surgical candidate with preoperative assessments such as labs and EKG performed per institutional standard and agree to be randomized to undergo open or robotic radical (or simple) hysterectomy.

NOTE: Simple hysterectomy will be allowed in patients who meet the following criteria:

• pelvic MRI must demonstrate a maximal tumor size of 2 cm or less AND
• less than 50% stromal invasion on MRI if tumor present or less than 10 mm of stromal invasion if an excisional (cold knife or LEEP) has been performed.

Submission of source documents in the GOG Partners Source Document Portal will be required prior to randomization for review and confirmation of simple hysterectomy being met (see Section 6.0 for instructions).

• Patient must be age 18 years or older.
• Patient must have ECOG performance status 0-1.
• Patient must have a negative urine pregnancy test within 30 days of surgery in pre-menopausal women.
• Patient must have signed an approved informed consent and authorization permitting the release of personal health information.

Exclusion criteria

• Patients with any tumor histology other than those listed above, specifically excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric type, endometrioid, clear cell, serous, signet ring, minimal deviation)
• Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
• Patient with inability to receive an MRI.
• Patients with a tumor size greater than 4cm or on MRI confirmed prior to randomization are excluded. Patients with definite evidence of vaginal/parametrial involvement on MRI are excluded; if MRI findings are not definitive, then clinical examination must also not reveal parametrial or vaginal extension).
• Patients with evidence of metastatic disease (imaging or histologically positive lymph nodes).
• Patients with a history of prior pelvic or abdominal radiotherapy.
• Patients with a prior malignancy < 5 years from enrollment with the exception of non-melanoma skin cancer.
• Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
• Patient compliance and geographic proximity that do not allow adequate follow-up.
• Patients with poorly controlled HIV with CD4 counts <500.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 137 centers

• Western Regional Medical Center LLC — Goodyear
• City of Hope — Duarte
• University of California San Diego Medical Center — Encinitas
• City of Hope Orange County Lennar Foundation Cancer — Irvine
• University of California San Diego Medical Center — La Jolla
• University of California San Diego Moores Cancer Center — La Jolla
• UCLA Gynecologic Oncology Clinic — Los Angeles
• Hoag Gynecologic Oncology — Newport Beach
• … and 129 more centers

South Korea · 10 centers

Center list to be confirmed — check the primary protocol.

Brazil · 6 centers

Center list to be confirmed — check the primary protocol.

Canada · 3 centers

Center list to be confirmed — check the primary protocol.

Publications

• Leitao MM Jr, Bixel KL, Chase DM, Quick A, McCormick C, Black D, Lim PC, Eskander RN, Gotlieb WH, LoCoco S, Martino MA, Walker JL, Copeland LJ, Monk BJ, Randall LM. ROCC/GOG-3043: a randomized controlled trial of robotic versus open surgery for early-stage cervical cancer. Int J Gynecol Cancer. 2025 Jul;35(7):101760. doi: 10.1016/j.ijgc.2025.101760. Epub 2025 Feb 28. PMID 40188007
• Boisen M, Guido R. Emerging Treatment Options for Cervical Dysplasia and Early Cervical Cancer. Clin Obstet Gynecol. 2023 Sep 1;66(3):500-515. doi: 10.1097/GRF.0000000000000790. Epub 2023 Jul 25. PMID 37650664

Identifiers

NCT: NCT04831580 · GOG-3043

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗