Biweekly Actinomycin-D Treatment or Multi-day Methotrexate Protocol in Low-risk Gestational Trophoblastic Neoplasia

NCT04562558 | Active Not Recruiting

• 1 other identifier: PUMCH-LRGTN-SINGLE DRUG-0222
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators conducted a randomized trial to study how well multi-day methotrexate protocol works compared to biweekly single-dose actinomycin D protocol in treating patients with low-risk gestational trophoblastic neoplasia. It is not yet known whether multi-day methotrexate protocol is as effective as biweekly single-dose actinomycin D protocol in treating patients with gestational trophoblastic neoplasia.

Conditions

Gestational Trophoblastic Tumor; Gestational Trophoblastic Neoplasia; Stage I Gestational Trophoblastic Tumor; Stage II Gestational Trophoblastic Tumor; Stage III Gestational Trophoblastic Tumor; Invasive Mole; Choriocarcinoma

Keywords

gestational trophoblastic neoplasia; actinomycin-D; methotrexate; low-risk

Outcome Measures

Primary Outcomes (2)

• Completely remission (CR) rate by single-agent

  Percentage of participants with complete response by single-agent chemotherapy. A complete response was defined as a normal hCG sustained over 3 weekly measurements.

  from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months

• Overall completely remission rate

  Percentage of participants with complete response by single-agent chemotherapy and those by second line multiple-drug chemotherapy after single-agent failure

  from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy or multi-agent chemotherapy，assessed up to 12 months

Secondary Outcomes (4)

• The duration needed to achieve complete remission after single-agent chemotherapy

  from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months

• The number of courses needed to achieve complete remission after single-agent chemotherapy

  from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months

• Incidence of Adverse Effects (Grade 3 or Higher)

  through study completion, an average of 3 year

• Effects on menstrual conditions and ovarian function

  Prior to treatment begin，and 6 month after single-agent chemotherapy completion, an average of 2 year

Study Arms (2)

Arm1-Methotrexate

EXPERIMENTAL

Patients receive methotrexate intramuscularly（50mg） on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days. Patients continue on treatment until beta HCG titer is below the institutional normal. Patients then receive 2-3 additional consolidation treatment. If the level of hCG become stationary for at least 2 course of single-agent chemotherapy or rise again, the patient will be referred to multi-course chemotherapy. FAV regimen is preferred, or EMA-CO regimen can also be selected if FAV is unavailable.

Drug: Methotrexate; Drug: Leucovorin

Arm 2-Dactinomycin

EXPERIMENTAL

Patients will receive IV pulse actinomycin-D (1.25mg/m2，2mg max dos) every 14 days. Patients continue on treatment until beta HCG titer is below the institutional normal. Patients then receive 2-3 additional consolidation treatment.If the level of hCG become stationary for at least 2 course of single-agent chemotherapy or rise again, the patient will be referred to multi-course chemotherapy. FAV regimen is preferred, or EMA-CO regimen can also be selected if FAV is unavailable.

Drug: Dactinomycin

Interventions

Methotrexate DRUG

50mg intramuscularly on Days 1, 3, 5, 7 . Repeat every 14 days

Also known as: MTX

Arm1-Methotrexate

Leucovorin DRUG

15mg intramuscularly on Days 2, 4, 6, 8. Repeat every 14 days

Also known as: Calcium folinate

Arm1-Methotrexate

Dactinomycin DRUG

1.25mg/m2 (2mg max dose)intravenous every 14 days.

Also known as: dactinomycin D

Arm 2-Dactinomycin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven low-risk gestational trophoblastic neoplasia (persistent hydatidiform mole or choriocarcinoma), defined as 1 of the following:
• Less than 10% decrease in the beta human chorionic gonadotropin (HCG) titer over 3 weekly titers
• Greater than 20% sustained rise in beta HCG titer over two consecutive weeks
• Histologically proven choriocarcinoma
• Stage I - III disease
• WHO risk score 0-4
• No prior chemotherapy for gestational trophoblastic neoplasia
• Signed informed consent
• Performance status - GOG 0-2
• Laboratory examination： WBC≥3.5×10(9)/L, Granulocyte count≥1.5×10(9)/L, Platelet count≥80×10(9)/L, serum bilirubin≤ 1.5 times the upper limit of normal, transaminase≤ 1.5 times the upper limit of normal, BUN, Creatinine≤ normal。 Fertile patients must use effective contraception during and for one year after study entry

You may not qualify if:

• Histologically confirmed placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)
• primary choriocarcinoma
• WHO risk score \>4
• Previous MTX treatment for suspected ectopic pregnancy
• With severe or uncontrolled internal disease, unable to receive chemotherapy;
• Concurrently participating in other clinical trials
• Unable or unwilling to sign informed consents;
• Unable or unwilling to abide by protocol.

Sponsors & Collaborators

• xiang yang: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (2)

• Jiang F, Guan CL, Jiao LZ, Xu T, Wan XR, Shi SS, Wu BB, Zhang X, Zhen L, Miao JW, Tian M, Du M, Li C, Feng FZ, Yang JJ, Ren T, Zhao J, Li Y, Zhang XQ, Lu X, Xiang Y. Efficacy and safety of biweekly single-dose actinomycin D versus multiday methotrexate in low-risk gestational trophoblastic neoplasia: a prospective multicenter randomized trial. Ann Oncol. 2025 Oct;36(10):1123-1131. doi: 10.1016/j.annonc.2025.06.006. Epub 2025 Jun 19.

  PMID: 40543844 DERIVED

• Jiang F, Mao MY, Xiang Y, Lu X, Guan CL, Jiao LZ, Wan XR, Feng FZ, Ren T, Yang JJ, Zhao J. Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial. BMC Cancer. 2023 Aug 23;23(1):784. doi: 10.1186/s12885-023-11225-2.

  PMID: 37612621 DERIVED

MeSH Terms

Conditions

Gestational Trophoblastic Disease; Hydatidiform Mole, Invasive; Choriocarcinoma

Interventions

Methotrexate; Leucovorin; Dactinomycin

Condition Hierarchy (Ancestors)

Trophoblastic Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Pregnancy Complications, Neoplastic; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hydatidiform Mole; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Heterocyclic Compounds, 3-Ring; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• yang xiang

  Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: the Director of Gynecological Oncology Center at Peking Union Medical College Hospital

Model Details: A prospective，multicenter，randomized trial with two arms

Study Record Dates

• First Submitted: September 13, 2020
• First Posted: September 24, 2020
• Study Start: September 29, 2020
• Primary Completion: November 11, 2024
• Study Completion: December 1, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

CN (1)