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RecruitingNCT04756713ReCureUpdated May 27, 2022

Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia

A Phase 3 interventional study of Uterine curettage and Chemotherapy in Gestational Trophoblastic Neoplasia, Molar Pregnancy and Gestational Trophoblastic Tumor, Non-Metastatic, sponsored by Brigham and Women's Hospital. Recruiting at 7 sites in Brazil. Open to female participants. Per ClinicalTrials.gov, last updated 2022-05-27.

Sponsored by Brigham and Women's Hospital · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
150
Allocation
Randomized
Sex
Female
01

Study summary

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

Read the 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.

02

Conditions studied

  • Gestational Trophoblastic Neoplasia
  • Molar Pregnancy
  • Gestational Trophoblastic Tumor, Non-Metastatic
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Investigator, Outcomes assessor)
Enrollment
150 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • ProcedureUterine curettage

    Manual or electric vacuum aspiration under ultrasound guidance.

  • DrugChemotherapy

    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.

05

What researchers measure

Primary outcomes

  1. Remission rate from primary therapy

    Undetectable hCG on weekly serum assay for at least three weeks

    Time frame: 3 years

Secondary outcomes

  1. Cycles to remission

    Total number of cycles of chemotherapy required to attain remission

    Time frame: 3 years

  2. Time to remission

    Time in days from randomization to remission

    Time frame: 3 years

  3. Need for multiagent chemotherapy

    Need for progression from single agent to multiagent chemotherapy

    Time frame: 3 years

  4. Relapse

    Re-elevation of hCG after achieving remission

    Time frame: 1 year

  5. Death

    Death from any cause

    Time frame: 1 year

06

Study locations

6 of 7 sites recruiting
  • Paulista State University UNESP
    Botucatu, Brazil
    • Izildinha Maestá · Contact
    Not yet recruiting
  • Campinas State University UNICAMP
    Campinas, Brazil
    • Daniela A Yela · Contact
    Recruiting
  • University of Caxias do Sul
    Caxias Do Sul, Brazil
    • José Mauro Madi · Contact
    Recruiting
  • Federal University of Ceará
    Ceará, Brazil
    • Cecília Maria Ponte · Contact
    Recruiting
  • Medical School of Santa Casa da Misericórdia de Porto Alegre
    Porto Alegre, Brazil
    • Elza -Maria Hartmann · Contact
    • Rodrigo Bernardes Cardoso · Principal investigator
    Recruiting
  • Maternidade Escola da Universidade Federal do Rio de Janeiro
    Rio de Janeiro, Brazil
    Recruiting
  • Federal University of São Paulo UNIFESP
    São Paulo, Brazil
    • Sue Yazaki Sun · Contact
    • Marcia Marcelino Ishigai · Principal investigator
    • Gustavo Rubino Focchi · Principal investigator
    Recruiting
07

References and documents

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. PubMed 27500329 ↗
  • 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. doi: 10.1097/AOG.0000000000003424. PubMed 30969220 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04756713
Lead sponsor
Brigham and Women's Hospital
Collaborators
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
Responsible party
Kevin Elias (Co-investigator, Brigham and Women's Hospital) — Principal investigator
First posted
Feb 16, 2021
Start date
Feb 11, 2021
Primary completion
Dec 31, 2024 (estimated)
Completion
Dec 31, 2025 (estimated)
Last update
May 27, 2022

Study contacts

MARCIO BARCELLOS, MD
Contact
mbezerrab@yahoo.com.br
(21)2556-9747
Antonio Braga, MD, PhD
study director · Maternidade Escola da Universidade Federal do Rio de Janeiro

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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