Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia

Phase 3

Recruiting

• Conditions: Molar Pregnancy; Gestational Trophoblastic Tumor, Non-Metastatic; Gestational Trophoblastic Neoplasia
• Interventions: Procedure: Uterine curettage; Drug: Chemotherapy

• Registration Number: NCT04756713
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

To evaluate the efficacy and safety of second uterine curettage in patients with low-risk non-metastatic GTN.

Detailed Description

This is a randomized, multicenter clinical trial including patients seen at one of 13 gestational trophoblastic disease reference centers in Brazil. Subjects are eligible if they have low-risk gestational trophoblastic neoplasia according to FIGO 2000 criteria and the FIGO/WHO prognostic risk score. The study includes two treatment arms: immediate treatment with single-agent chemotherapy (center choice of agent) or second uterine curettage. The primary outcome is the rate of primary remission. Secondary outcomes are the number of chemotherapy cycles required to achieve remission, rate of primary chemotherapy resistance, rate of relapse, and overall survival.

Study Timeline

• Study Start: 2021-02-11
• Study First Submitted: 2021-02-12
• Study First Submitted QC: 2021-02-12
• Study First Posted: 2021-02-16
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-23
• Last Update Posted: 2022-05-27
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 150

Inclusion Criteria

• Histopathological diagnosis of molar pegnancy according to the morphological criteria described by Sebire et al., who meet the diagnostic criteria for low-risk non-metastatic GTN according to FIGO 2000 criteria

Exclusion Criteria

1. High risk GTN (FIGO risk score ≥ 7) or metastatic disease at diagnosis of GTN (stage II, III or IV);
2. Histopathological diagnosis of choriocarcinoma, placental site trophoblastic or epithelioid trophoblastic tumor at the second curettage;
3. Previous chemotherapy treatment;
4. Level of hCG at the time of GTN diagnosis less than 20 IU/L (to minimize the risk of inclusion of patients with false positive hCG, either by cross-reaction with pituitary hormones or by the presence of circulating heterophilic antibodies);
5. Relapsed GTN;
6. Incomplete medical records.
7. Loss to follow-up;
8. Voluntary desire to stop participating in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Uterine evacuation	Uterine curettage	Patients randomized to undergo a second curettage will undergo manual or electronic vacuum aspiration under ultrasound guidance. Following discharge after the second curettage patients will return to weekly hCG monitoring. If hCG levels are decreasing, patients will remain on weekly hCG follow-up until the first normal hCG (\<5 IU/L) is achieved. Then they will have monthly hCG monitoring for 12 months. If patients do not attain remission and develop persistent GTN as established by FIGO 2000, the tumor will be re-staged and appropriate chemotherapy will be initiated.
Chemotherapy	Chemotherapy	Patients allocated to receive conventional chemotherapy will be treated with methotrexate (1 mg/kg intramuscular) with rescue of folinic acid (15mg orally). In cases of chemoresistance, second-line chemotherapy will be performed with actinomycin-D (Act-D) 1.25 mg intravenous pulse every 14 days. The third line of chemotherapy will be the EMA/CO regimen (reserving the EP / EMA regimen (E, cisplatin, MTX / Act-D) for the fourth line.

Primary Outcome Measures

Name	Time	Method
Remission rate from primary therapy	3 years	Undetectable hCG on weekly serum assay for at least three weeks

Secondary Outcome Measures

Name	Time	Method
Cycles to remission	3 years	Total number of cycles of chemotherapy required to attain remission
Time to remission	3 years	Time in days from randomization to remission
Death	1 year	Death from any cause
Need for multiagent chemotherapy	3 years	Need for progression from single agent to multiagent chemotherapy
Relapse	1 year	Re-elevation of hCG after achieving remission

Trial Locations

Locations (7)

Paulista State University UNESP; 🇧🇷 Botucatu, Brazil

Campinas State University UNICAMP; 🇧🇷 Campinas, Brazil

Maternidade Escola da Universidade Federal do Rio de Janeiro; 🇧🇷 Rio de Janeiro, Brazil

Federal University of Ceará; 🇧🇷 Ceará, Brazil

Medical School of Santa Casa da Misericórdia de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

University of Caxias do Sul; 🇧🇷 Caxias Do Sul, Brazil

Federal University of São Paulo UNIFESP; 🇧🇷 São Paulo, Brazil