Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia

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

Detailed Description
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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.

Official Title
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Impact of Second Uterine Evacuation in Women With Non-metastatic, Low-risk Gestational Trophoblastic Neoplasia: A Phase III Trial

Conditions
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Gestational Trophoblastic Neoplasia, Molar Pregnancy, Gestational Trophoblastic Tumor, Non-Metastatic

Intervention / Treatment
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* Procedure: Uterine curettage
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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: High risk GTN (FIGO risk score ≥ 7) or metastatic disease at diagnosis of GTN (stage II, III or IV); Histopathological diagnosis of choriocarcinoma, placental site trophoblastic or epithelioid trophoblastic tumor at the second curettage; Previous chemotherapy treatment; 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); Relapsed GTN; Incomplete medical records. Loss to follow-up; Voluntary desire to stop participating in the study.
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: Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemotherapy<br>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. | Drug: Chemotherapy<br>* conventional chemotherapy will be treated with MTX (1 mg/kg intramuscular) with rescue of FA (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.<br>|
| Experimental: Uterine evacuation<br>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. | Procedure: Uterine curettage<br>* Manual or electric vacuum aspiration under ultrasound guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate from primary therapy | Undetectable hCG on weekly serum assay for at least three weeks | 3 years | 

Secondary Outcome Measures

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