Clinical trial NCT06489795: German-funded Laparoscopic Approach to Cervical Cancer
Official title: A Randomized Clinical Trial Comparing Laparoscopic or Robot-assisted Radical/Simple Hysterectomy Versus Abdominal Radical/Simple Hysterectomy in Patients With Early-stage Cervical Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cervical Cancer
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
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: German Cancer Aid
First posted: 2024-07-08
Enrollment: 756
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional, multicenter, open-label, randomized, controlled non-inferiority trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Disease-free survival
timeFrame: up to year 5
Secondary outcomes:
measure: Overall survival
timeFrame: up to year 5
measure: Disease recurrence
timeFrame: up to year 5 starting 6 months post-surgery
measure: Health Related Quality of Life (HRQoL): Core questionnaire
timeFrame: up to year 5
measure: Health Related Quality of Life (HRQoL): Cervical cancer questionnaire
timeFrame: up to year 5
measure: Health Related Quality of Life (HRQoL): General health status
timeFrame: up to year 5
measure: Health Related Quality of Life (HRQoL): Sexual activity
timeFrame: up to year 5
measure: Lymphatic side effects: Investigator assessment
timeFrame: up to year 5
measure: Lymphatic side effects: Patient assessment
timeFrame: up to year 5
measure: Complications and treatment-associated morbidity
timeFrame: up to one year after surgery
measure: Serious adverse events
timeFrame: up to one year after surgery
measure: Health care costs: Cost-effectiveness
timeFrame: up to year 5
measure: Health care costs: Direct cost assessment
timeFrame: up to year 5
measure: Health care costs: Cost-utility analysis
timeFrame: up to year 5
Other outcomes:
Locations:
city: Ludwigsburg
country: Germany
facility: Ludwigsburg Hospital, Department of Gynecology and Obstetrics
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: University Medical Center Tübingen, Department of Gynecology
state: Baden-Württemberg
city: Berlin Schöneberg
country: Germany
facility: Vivantes Auguste-Viktoria-Hospital, Department of Gynecology
state: Berlin
city: Bad Homburg vor der Höhe
country: Germany
facility: Hochtaunus-Clinics Bad Homburg, Department of Gynecology
state: Hesse
city: Göttingen
country: Germany
facility: University Medical Center Göttingen, Department of Gynecology and Obstetrics
state: Lower Saxony
city: Hannover
country: Germany
facility: Hannover Medical School, Department of Gynecology and Obstetrics
state: Lower Saxony
city: Lüneburg
country: Germany
facility: Hospital Lüneburg, Department of Gynecology
state: Lower Saxony
city: Bielefeld
country: Germany
facility: Hospital Bielefeld - Center, Department of Gynecology
state: North Rhine-Westphalia
city: Düsseldorf
country: Germany
facility: University Medical Center Düsseldorf, Department of Gynecology and Obstetrics
state: North Rhine-Westphalia
city: Wesel
country: Germany
facility: Protestant Hospital Wesel, Gynecological Cancer Center
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: University Medical Center Mainz, Department of Obstetrics and Gynecology
state: Rhineland Palatinate
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein, Campus Kiel, Department of Gynecology and Obstetrics
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Martin Luther Hospital Berlin, Department of Gynecology and Obstetrics
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf, Department of Gynecology
Study officials:
affiliation: Hannover Medical School, Department of Gynecology and Obstetrics
name: Peter Hillemanns, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: