LESs Surgical Radicality for EaRly Stage Cervical Cancer

Study Overview
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Brief Summary
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This study is an open-label, multicenter, randomized, phase II non-inferiority trial (proof of concept study). Its purpose is to evaluate the safety and efficacy of extrafascial hysterectomy plus pelvic-lymph node dissection compared with the standard modified radical hysterectomy in patients with stage IA2-IB1 cervical cancer ≤ 2cm.

Detailed Description
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The purpose of this study is to evaluate the safety and efficacy of extrafascial hysterectomy compared with modified radical hysterectomy, both plus level 1 pelvic lymph-node dissection, in patients with early stage IA2-IB1 cervical cancer ≤ 2cm. The experimental procedure will be considered to be promising for treatment of stage IA2-IB1 cervical cancer ≤ 2cm if the Bayesian posterior probability of the difference of the 3-y DFS rate is less than the non-inferiority margin of 5% is at least 50%. Thus, using this proof of concept design, the planned sample size is 40, with 20 cases per arm, which provides 72% chance of satisfying the above criteria, under the hypothesis that the lowest 3-y DFS rate in each arm is 90%. As required, adjuvant therapy will include cisplatin-based chemo-radiation or pelvic radiation alone (EBRT +/- intracavitary brachytherapy) indicated according to the #GOG92 and #GOG109 criteria.

Official Title
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A Proof of Concept Non-inferiority Trial Evaluating the Safety and Efficacy of Extrafascial Hysterectomy Plus Pelvic Lymph-node Dissection in Patients With Stage IA2-IB1 Cervical Cancer ≤ 2cm

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Procedure: Extrafascial Hysterectomy
* Procedure: Modified radical hysterectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed adenocarcinoma, squamous, or adenosquamous cancer of the cervix by LEEP, cone or cervical biopsy; Aged between 18 and 70 years; performance status 0-2 (ECOG, Eastern Cooperative Oncology Group) and / or greater than 70 points by the Karnofsky scale; FIGO early stage IA2-IB1 ≤ 2cm; Appropriated cardio-respiratory, hepato-renal and hematological reserves; and Signing of the Consent Form. Exclusion Criteria: Limiting systemic comorbidities including neuro-psychiatric disorders or obesity; Apparent or confirmed uncontrolled infections; Other malignancies in activity; Previous radiation or chemotherapy treatment or major pelvic surgery; History of drug allergies, and pregnancy or breast feeding; and Evidence of more extensive disease at the time of surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Proof of concept design (phase II non-inferiority trial)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Extrafascial Hysterectomy<br>Type A hysterectomy with 1 - 2cm of vaginal cuff plus level 1 pelvic lymph-node dissection according to Querleu and Morrow classification. | Procedure: Extrafascial Hysterectomy<br>* Hysterectomy plus Pelvic Lymph-Node Dissection<br>|
| Active Comparator: Modified radical hysterectomy<br>Type B2 hysterectomy with 1 - 2cm of vaginal cuff plus level 1 pelvic lymph-node dissection according to Querleu and Morrow classification. | Procedure: Modified radical hysterectomy<br>* Hysterectomy plus Pelvic Lymph-Node Dissection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (3-y DFS) | Time from surgery to recurrence | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related adverse events (surgical) | Surgical morbidity and mortality | 90 days | 
| Patient reported QoL | QoL according to EORTC C30 questionnaire (v3.0) | Base-line and 6 months. | 
| Rates of using adjuvant therapy | Cisplatin-based chemo-radiation or pelvic radiation alone (EBRT +/- intracavitary brachytherapy) indicated according to the #GOG92 and #GOG109 criteria | 90 days | 
| Overall survival (3-y OS) | Time from surgery to death of any cause | 3 years |