German-funded Laparoscopic Approach to Cervical Cancer

Hannover Medical School756 enrolled

Overview

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.

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.

Interventions

Laparoscopic or robot-assisted radical/simple hysterectomyPROCEDURE

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.

Abdominal radical/simple hysterectomyPROCEDURE

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.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (14)

Ludwigsburg Hospital, Department of Gynecology and Obstetrics

Ludwigsburg, Baden-Wurttemberg, Germany

RECRUITING

University Medical Center Tübingen, Department of Gynecology

Tübingen, Baden-Wurttemberg, Germany

RECRUITING

Hochtaunus-Clinics Bad Homburg, Department of Gynecology

Bad Homburg, Hesse, Germany

RECRUITING

University Medical Center Göttingen, Department of Gynecology and Obstetrics

Göttingen, Lower Saxony, Germany

RECRUITING

Hannover Medical School, Department of Gynecology and Obstetrics

Hanover, Lower Saxony, Germany

RECRUITING

Hospital Lüneburg, Department of Gynecology

Lüneburg, Lower Saxony, Germany

RECRUITING

Hospital Bielefeld - Center, Department of Gynecology

Bielefeld, North Rhine-Westphalia, Germany

RECRUITING

University Medical Center Düsseldorf, Department of Gynecology and Obstetrics

Düsseldorf, North Rhine-Westphalia, Germany

RECRUITING

Protestant Hospital Wesel, Gynecological Cancer Center

Wesel, North Rhine-Westphalia, Germany

RECRUITING

University Medical Center Mainz, Department of Obstetrics and Gynecology

Mainz, Rhineland-Palatinate, Germany

RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

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.

Time frame: up to year 5

Secondary Outcomes

Overall survival

Overall survival (OS) is defined as the time from randomization to death from any cause.

Time frame: 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.

Time frame: up to year 5 starting 6 months post-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)

Time frame: 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)

Time frame: 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

Time frame: 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).

Time frame: 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)

Time frame: 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.

Time frame: up to year 5

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.

Time frame: 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.

Time frame: up to one year after surgery

Health care costs: Cost-effectiveness

Cost-effectiveness will be determined as incremental cost-effectiveness ratios.

Time frame: up to year 5

Health care costs: Direct cost assessment

Direct costs will be assessed via internal accounting and billing systems within the hospitals.

Time frame: up to year 5

Health care costs: Cost-utility analysis

Quality-adjusted life years (QALY) calculations will be used for a cost-utility analysis.

Time frame: up to year 5

German-funded Laparoscopic Approach to Cervical Cancer

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts