Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia (ReCure)

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

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

Study Overview

• Status: Recruiting
• Conditions: Gestational Trophoblastic Neoplasia; Molar Pregnancy; Gestational Trophoblastic Tumor, Non-Metastatic
• Intervention / Treatment: Drug: Chemotherapy; Procedure: Uterine curettage

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 Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: MARCIO BARCELLOS, MD; Phone Number: (21)2556-9747; Email: mbezerrab@yahoo.com.br

Study Locations

• Brazil
  • Botucatu, Brazil
    • Not yet recruiting
    • Paulista State University UNESP
    • Contact: Izildinha Maestá
  • Campinas, Brazil
    • Recruiting
    • Campinas State University UNICAMP
    • Contact: Daniela A Yela
  • Caxias Do Sul, Brazil
    • Recruiting
    • University of Caxias do Sul
    • Contact: José Mauro Madi
  • Ceará, Brazil
    • Recruiting
    • Federal University of Ceará
    • Contact: Cecília Maria Ponte
  • Porto Alegre, Brazil
    • Recruiting
    • Medical School of Santa Casa da Misericórdia de Porto Alegre
    • Contact: Elza -Maria Hartmann
    • Principal Investigator: Rodrigo Bernardes Cardoso
  • Rio de Janeiro, Brazil
    • Recruiting
    • Maternidade Escola da Universidade Federal do Rio de Janeiro
    • Contact: Marcio Barcellos, MD; Email: mbezerrab@yahoo.com.br
    • Contact: Antonio Braga, MD; Email: bragamed@yahoo.com.br
  • São Paulo, Brazil
    • Recruiting
    • Federal University of São Paulo UNIFESP
    • Contact: Sue Yazaki Sun
    • Principal Investigator: Marcia Marcelino Ishigai
    • Principal Investigator: Gustavo Rubino Focchi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Chemotherapy; 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.
Experimental: Uterine evacuation; 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; Manual or electric vacuum aspiration under ultrasound guidance.

What is the study measuring?

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
Death	Death from any cause	1 year
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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Universidade Federal do Rio de Janeiro; Maternidade Escola da Universidade Federal do Rio de Janeiro; Federal University of Ceará; Federal University of São Paulo UNIFESP; Campinas State University UNICAMP; Paulista State University UNESP BOTUCATU; Medical School of Santa Casa da Misericórdia de Porto Alegr; University of Caxias do Sul
• Investigators: Study Director: Antonio Braga, MD, PhD, Maternidade Escola da Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Osborne RJ, Filiaci VL, Schink JC, Mannel RS, Behbakht K, Hoffman JS, Spirtos NM, Chan JK, Tidy JA, Miller DS. Second Curettage for Low-Risk Nonmetastatic Gestational Trophoblastic Neoplasia. Obstet Gynecol. 2016 Sep;128(3):535-542. doi: 10.1097/AOG.0000000000001554.
• Hemida R, Vos EL, El-Deek B, Arafa M, Toson E, Burger CW, van Doorn HC. Second Uterine Curettage and the Number of Chemotherapy Courses in Postmolar Gestational Trophoblastic Neoplasia: A Randomized Controlled Trial. Obstet Gynecol. 2019 May;133(5):1024-1031. doi: 10.1097/AOG.0000000000003232. Erratum In: Obstet Gynecol. 2019 Sep;134(3):652.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Pregnancy Complications; Pregnancy Complications, Neoplastic; Neoplasms; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Hydatidiform Mole
• Other Study ID Numbers: RECURE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No