ReCure: Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04756713
• Collaborator: Maternidade Escola da Universidade Federal do Rio de Janeiro (Other), Universidade Federal do Rio de Janeiro (Other), Federal University of Ceará (Other), Federal University of São Paulo UNIFESP (Other), Campinas State University UNICAMP (Other), Paulista State University UNESP BOTUCATU (Other), Medical School of Santa Casa da Misericórdia de Porto Alegr (Other), University of Caxias do Sul (Other)
• Enrollment: 150
• Locations: 7
• Arms: 2
• Anticipated Duration (Months): 58.6
• Patients Per Site: 21.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Gestational Trophoblastic Neoplasia; Molar Pregnancy; Gestational Trophoblastic Tumor, Non-Metastatic	Procedure: Uterine curettage; Drug: Chemotherapy	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: RandomizedRandomized
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: Treatment assignments are made by a remote investigator not involved in the clinical care of the patient using a coded key with random block sizes.
• Primary Purpose: Treatment
• Official Title: Impact of Second Uterine Evacuation in Women With Non-metastatic, Low-risk Gestational Trophoblastic Neoplasia: A Phase III Trial
• Actual Study Start Date: Feb 11, 2021
• Anticipated Primary Completion Date: Dec 31, 2024
• Anticipated Study Completion Date: Dec 31, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Remission rate from primary therapy [3 years]

   Undetectable hCG on weekly serum assay for at least three weeks

Secondary Outcome Measures

1. Cycles to remission [3 years]

   Total number of cycles of chemotherapy required to attain remission

2. Time to remission [3 years]

   Time in days from randomization to remission

3. Need for multiagent chemotherapy [3 years]

   Need for progression from single agent to multiagent chemotherapy

4. Relapse [1 year]

   Re-elevation of hCG after achieving remission

5. Death [1 year]

   Death from any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Paulista State University UNESP	Botucatu		Brazil
2	Campinas State University UNICAMP	Campinas		Brazil
3	University of Caxias do Sul	Caxias Do Sul		Brazil
4	Federal University of Ceará	Ceará		Brazil
5	Medical School of Santa Casa da Misericórdia de Porto Alegre	Porto Alegre		Brazil
6	Maternidade Escola da Universidade Federal do Rio de Janeiro	Rio de Janeiro		Brazil
7	Federal University of São Paulo UNIFESP	São Paulo		Brazil

Sponsors and Collaborators

• Brigham and Women's Hospital
• Maternidade Escola da Universidade Federal do Rio de Janeiro
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Kevin Elias, Co-investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04756713
• Other Study ID Numbers: ReCure
• First Posted: Feb 16, 2021
• Last Update Posted: May 27, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Hydatidiform Mole

Study Results

No Results Posted as of May 27, 2022