German-funded Laparoscopic Approach to Cervical Cancer (G-LACC)

A Randomized Clinical Trial Comparing Laparoscopic or Robot-assisted Radical/Simple Hysterectomy Versus Abdominal Radical/Simple Hysterectomy in Patients With Early-stage Cervical Cancer

The G-LACC trial is a prospective, interventional, multicenter, open-label, randomized and controlled non-inferiority operative trial.

The main goal of this clinical trial is to evaluate the non-inferiority of minimally invasive radical hysterectomy in contrast to abdominal radical hysterectomy in patients with early-stage cervical cancer. In the case of SHAPE criteria, surgery may also be performed as minimally invasive or abdominal simple hysterectomy. The primary criterion for assessment is disease-free survival (DFS). As secondary outcomes, overall survival (OS), disease recurrence, quality of life, intra-/postoperative complications, and serious adverse events are recorded for assessment.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Procedure: Laparoscopic or robot-assisted radical/simple hysterectomy; Procedure: Abdominal radical/simple hysterectomy

Detailed Description

Eligible patients will be randomly allocated to both treatment arms in a 1:1 ratio. Within an accrual period of 4 years, 378 patients will be included per arm (756 in total) across all sites. The Follow-up period after surgery will take a minimum of 5 years.

In the standard arm, radical hysterectomy is performed as per standard technique abdominal radical hysterectomy (Piver type 2 or 3 or Querleu & Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. Surgery includes pelvic lymph node dissection or optional sentinel lymph node biopsy (SNB) according to current guidelines in both arms.

In the experimental arm, radical hysterectomy is performed as per standard conventional 2D/3D laparoscopic or robotic assisted technique (Querleu & Morrow Type B or C) with salpingectomy +/- oophorectomy. Ovaries may be removed or preserved +/- transposition. The following protective measures are mandatory for the minimally invasive arm: LEEP/conization prior to randomization or vaginal closure prior to colpotomy. Transcervical manipulators are not permitted. Use of uterus manipulators/ cervical adapter (without transcervical device) is allowed only after LEEP/conization. Meticulous dissection of pelvic (sentinel) lymph nodes including use of endobags and avoiding the dissemination of cancer cells will be implemented (tumor hygiene).

Due to the positive results of the SHAPE trial published at Plante et al. NEJM 2024, in both arms simple hysterectomy can be considered for patients with low-risk early-stage cervical cancer (SHAPE criteria: tumor < 2 cm, < 10 mm depth of stromal invasion (LEEP/cone) BUT has to be determined BEFORE randomization. Simple hysterectomy has to be performed as extrafascial hysterectomy and the preparation of a max. 5 mm vaginal cuff is required to ensure negative margins. Surgery can be performed including removal of the sentinel lymph nodes following the concept of sentinel lymph node biopsy (SNB) and according to the current guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 756
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Hillemanns, Prof. Dr.; Phone Number: 6144 +49 (0) 511 532; Email: frauenklinik@mh-hannover.de
• Study Contact Backup: Name: Oliver Papp; Phone Number: 7234 +49 (0) 176 1532; Email: g-lacc.zks@mh-hannover.de

Study Locations

• Germany
  • Berlin, Germany, 14193
    • Recruiting
    • Martin Luther Hospital Berlin, Department of Gynecology and Obstetrics
    • Contact: Uwe A. Ulrich, Prof. Dr.; Phone Number: 3311 +49 (0) 30 8955; Email: gynaekologie.martin-luther@jsd.de
  • Hamburg, Germany, 20246
    • Recruiting
    • University Medical Center Hamburg-Eppendorf, Department of Gynecology
    • Contact: Jan Dieckmann, Dr.; Phone Number: 23800 +49 (0) 40 7410; Email: frauenklinik@uke.de
  • Baden-Württemberg
    • Ludwigsburg, Baden-Württemberg, Germany, 71640
      • Recruiting
      • Ludwigsburg Hospital, Department of Gynecology and Obstetrics
      • Contact: Sebastian Berlit, Prof. Dr.; Phone Number: 67601 +49 (0) 7141 99
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • University Medical Center Tübingen, Department of Gynecology
      • Contact: Sara Y. Brucker, Prof. Dr.; Phone Number: 80791 +49 (0) 7071 29; Email: frauenklinik@med.uni-tuebingen.de
  • Berlin
    • Berlin Schöneberg, Berlin, Germany, 12157
      • Recruiting
      • Vivantes Auguste-Viktoria-Hospital, Department of Gynecology
      • Contact: Farnaz Jakubek; Phone Number: 2402 +49 (0) 30 130 20; Email: gyn-ambulanz.avk@vivantes.de
  • Hesse
    • Bad Homburg vor der Höhe, Hesse, Germany, 61352
      • Recruiting
      • Hochtaunus-Clinics Bad Homburg, Department of Gynecology
      • Contact: Dominik Denschlag, Prof. Dr.; Phone Number: 2580 +49 (0) 6172 14; Email: sekretariat-frauenklinik@hochtaunus-kliniken.de
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Recruiting
      • University Medical Center Göttingen, Department of Gynecology and Obstetrics
      • Contact: Julia Gallwas, Prof. Dr.; Phone Number: 2501 +49 (0) 551 396; Email: direktion.ufk@med.uni-goettingen.de
    • Hannover, Lower Saxony, Germany, 30625
      • Recruiting
      • Hannover Medical School, Department of Gynecology and Obstetrics
      • Contact: Peter Hillemanns, Prof. Dr.; Phone Number: 6144 +49 (0) 511 532; Email: frauenklinik@mh-hannover.de
      • Contact: Hermann Hertel, Prof. Dr.; Phone Number: 9760 +49 (0) 511 532; Email: frauenklinik@mh-hannover.de
    • Lüneburg, Lower Saxony, Germany, 21339
      • Recruiting
      • Hospital Lüneburg, Department of Gynecology
      • Contact: Peter Dall, Prof. Dr.; Phone Number: 2231 +49 (0) 4131 77; Email: frauenklinik@klinikum-lueneburg.de
  • North Rhine-Westphalia
    • Bielefeld, North Rhine-Westphalia, Germany, 33604
      • Recruiting
      • Hospital Bielefeld - Center, Department of Gynecology
      • Contact: Werner Bader, Prof. Dr.; Phone Number: 3271 +49 (0) 521 581; Email: frauenklinik@klinikumbielefeld.de
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Recruiting
      • University Medical Center Düsseldorf, Department of Gynecology and Obstetrics
      • Contact: Tanja Fehm, Prof. Dr.; Phone Number: 17501 +49 (0) 211 81; Email: direktion.frauenklinik@med.uni-duesseldorf.de
    • Wesel, North Rhine-Westphalia, Germany, 46485
      • Recruiting
      • Protestant Hospital Wesel, Gynecological Cancer Center
      • Contact: Nicole Sigrist-Uhl; Phone Number: 2700 +49 (0) 281 106; Email: gynaekologie@evkwesel.de
  • Rhineland Palatinate
    • Mainz, Rhineland Palatinate, Germany, 55131
      • Recruiting
      • University Medical Center Mainz, Department of Obstetrics and Gynecology
      • Contact: Roxana Schwab, PD Dr.; Phone Number: 7574 +49 (0) 6131 17; Email: uct-hotline@unimedizin-mainz.de
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Recruiting
      • University Hospital Schleswig-Holstein, Campus Kiel, Department of Gynecology and Obstetrics
      • Contact: Ibrahim Alkatout, Prof. Dr.; Phone Number: 21407 +49 (0) 431 500; Email: Frauenklinik.Kiel@uksh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed primary adenocarcinoma, squamous cell carcinoma or adenosquamous carcinoma of the uterine cervix
2. Patients with FIGO stage IA2, IB1, or IB2 disease (<4 cm)

3. Patients undergoing radical hysterectomy according either to Type II or III (Piver Classification) or to Type B or C (Querleu and Morrow classification)

   OR

   Simple hysterectomy can be considered for patients with low-risk early-stage cervical cancer (SHAPE criteria: tumor < 2cm, < 10 mm depth of stromal invasion (LEEP/cone). Simple hysterectomy has to be performed as extrafascial hysterectomy and the preparation of a max. 5mm vaginal cuff is required to ensure negative margins.

4. Performance status of ECOG 0-1
5. Patient must be suitable candidates for surgery with preoperative MRI and available for assessment of serious adverse events up to one year post-surgery
6. Patients who have signed an approved Informed Consent
7. Patients with a prior malignancy only if > 5 years previous with no evidence of disease
8. Females, aged 18 years or older

Exclusion Criteria:

1. Any histology other than an adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the uterine cervix
2. Tumor size of 4 cm and greater, estimated by either magnetic resonance imaging (MRI) or clinical examination
3. FIGO stage IB3 - IV
4. Patients with a history of pelvic or abdominal radiotherapy
5. Patients with evidence of metastatic disease by conventional imaging studies, enlarged pelvic or aortic lymph nodes > 2 cm, or histologically positive lymph nodes
6. Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
7. Patients unable to withstand prolonged lithotomy and steep Trendelenburg position
8. Patient compliance and geographic proximity that do not allow adequate follow-up
9. Women who are pregnant
10. Patients with contraindications to surgery
11. Patients with secondary invasive neoplasm in the last 5 years (except non-melanoma skin cancer, breast cancer T1 N0 M0 grade 1 or 2 without any signs of recurrence or activity)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental intervention: Laparoscopic or robot-assisted radical/simple hysterectomy; In the experimental arm, patients with early-stage cervical cancer will be treated by using laparoscopic or robot-assisted radical/simple hysterectomy.	Procedure: Laparoscopic or robot-assisted radical/simple hysterectomy; In the experimental arm, patients with early-stage cervical cancer will be treated by using laparoscopic or robot-assisted radical, or in the case of SHAPE criteria, simple hysterectomy.
Other: Control intervention: Abdominal radical/simple hysterectomy; In the control arm, abdominal radical/simple hysterectomy (ARH) will be used as standard therapy.	Procedure: Abdominal radical/simple hysterectomy; In the control arm, patients with early-stage cervical cancer will be treated by using abdominal radical, or in the case of SHAPE criteria, simple hysterectomy as standard therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival (DFS) is defined as the time from randomization to disease recurrence or death from any course (whichever occurs first). The date of disease recurrence is defined as the date of biopsy.	up to year 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) is defined as the time from randomization to death from any cause.	up to year 5
Disease recurrence	The date of recurrence of disease is defined as the date of biopsy. A suspicion of disease recurrence (clinical or by imaging) should be verified by histopathological assessment. Disease recurrence will be assessed and recorded at each follow-up visit starting 6 months post-surgery.	up to year 5 starting 6 months post-surgery
Complications and treatment-associated morbidity	Treatment-related intraoperative complications are recorded on the day of surgery according to Rosenthal's definition. Treatment-related postoperative complications are recorded from the day of surgery until one year after surgery.	up to one year after surgery
Serious adverse events	Serious adverse events (SAEs) will be captured from the day of surgery until one year post surgery. Treatment-related SAEs are documented as intra-/postoperative complications according to Outcome 5.	up to one year after surgery
Health Related Quality of Life (HRQoL): Core questionnaire	Health Related Quality of Life (HRQoL) will be assessed by using the validated questionnaire European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-30)	up to year 5
Health Related Quality of Life (HRQoL): Cervical cancer questionnaire	Health Related Quality of Life (HRQoL) will be assessed by using the validated questionnaire EORTC QLQ Cervical Cancer Module (EORTC QLQ-CX24)	up to year 5
Health Related Quality of Life (HRQoL): General health status	Health Related Quality of Life (HRQoL) will be assessed by using the validated questionnaire EuroQoL EQ-5D-3L	up to year 5
Health Related Quality of Life (HRQoL): Sexual activity	Health Related Quality of Life (HRQoL) will be assessed by using the validated sexual activity questionnaires (SAQ).	up to year 5
Lymphatic side effects: Investigator assessment	Lymphatic side effects will be assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE 3.0)	up to year 5
Lymphatic side effects: Patient assessment	Lymphatic side effects will be assessed by the patient using the Lymphoedema Quality-of-Life (LYMQOL) questionnaire.	up to year 5
Health care costs: Cost-effectiveness	Cost-effectiveness will be determined as incremental cost-effectiveness ratios.	up to year 5
Health care costs: Direct cost assessment	Direct costs will be assessed via internal accounting and billing systems within the hospitals.	up to year 5
Health care costs: Cost-utility analysis	Quality-adjusted life years (QALY) calculations will be used for a cost-utility analysis.	up to year 5

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: German Cancer Aid
• Investigators: Principal Investigator: Peter Hillemanns, Prof. Dr., Hannover Medical School, Department of Gynecology and Obstetrics

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Estimated): July 1, 2033
• Study Completion (Estimated): January 1, 2034

Study Registration Dates

• First Submitted: June 23, 2024
• First Submitted That Met QC Criteria: July 4, 2024
• First Posted (Actual): July 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: cervical cancer FIGO stage IA2; cervical cancer FIGO stage IB1; cervical cancer FIGO stage IB2; laparoscopic or robot-assisted radical/simple hysterectomy; abdominal radical/simple hysterectomy; simple hysterectomy in the case of SHAPE criteria
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: G-LACC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No