Cervical Cancer
Conditions
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
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.
Interventions
PROCEDURELaparoscopic 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.
PROCEDUREAbdominal 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.
Sponsors
German Cancer Aid
Hannover Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Interventional, multicenter, open-label, randomized, controlled non-inferiority trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | up to year 5 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease recurrence | up to year 5 starting 6 months post-surgery | 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. |
| Health Related Quality of Life (HRQoL): Core questionnaire | up to year 5 | 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) |
| Health Related Quality of Life (HRQoL): Cervical cancer questionnaire | up to year 5 | Health Related Quality of Life (HRQoL) will be assessed by using the validated questionnaire EORTC QLQ Cervical Cancer Module (EORTC QLQ-CX24) |
| Health Related Quality of Life (HRQoL): General health status | up to year 5 | Health Related Quality of Life (HRQoL) will be assessed by using the validated questionnaire EuroQoL EQ-5D-3L |
| Health Related Quality of Life (HRQoL): Sexual activity | up to year 5 | Health Related Quality of Life (HRQoL) will be assessed by using the validated sexual activity questionnaires (SAQ). |
| Lymphatic side effects: Investigator assessment | up to year 5 | Lymphatic side effects will be assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE 3.0) |
| Overall survival | up to year 5 | Overall survival (OS) is defined as the time from randomization to death from any cause. |
| Complications and treatment-associated morbidity | up to one year after surgery | 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. |
| Serious adverse events | up to one year after surgery | 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. |
| Health care costs: Cost-effectiveness | up to year 5 | Cost-effectiveness will be determined as incremental cost-effectiveness ratios. |
| Health care costs: Direct cost assessment | up to year 5 | Direct costs will be assessed via internal accounting and billing systems within the hospitals. |
| Health care costs: Cost-utility analysis | up to year 5 | Quality-adjusted life years (QALY) calculations will be used for a cost-utility analysis. |
| Lymphatic side effects: Patient assessment | up to year 5 | Lymphatic side effects will be assessed by the patient using the Lymphoedema Quality-of-Life (LYMQOL) questionnaire. |
Countries
Germany
Contacts
Primary ContactPeter Hillemanns, Prof. Dr.
Backup ContactOliver Papp
Outcome results
None listed