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

NCT04562558Active, Not RecruitingNAINTERVENTIONAL

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.

Key Facts

Lead Sponsor

xiang yang

Enrollment

228

Start Date

2020-09-29

Completion Date

2024-11-11

Study Type

INTERVENTIONAL

Official Title

A Prospective，Multicenter，Randomized Trial of Biweekly Single-dose Actinomycin-D Versus Multi-day Methotrexate Protocol for the Treatment of Low-risk Gestational Trophoblastic Neoplasia

Interventions

MethotrexateLeucovorinDactinomycin

Conditions

Gestational Trophoblastic TumorGestational Trophoblastic NeoplasiaStage I Gestational Trophoblastic TumorStage II Gestational Trophoblastic TumorStage III Gestational Trophoblastic TumorInvasive MoleChoriocarcinoma

Eligibility

Age Range

18 Years – 75 Years

Sex

FEMALE

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Outcome Measures

Primary Outcomes

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.

Time frame: 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

Time frame: 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

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

The duration needed to achieve complete remission after single-agent in two arms

Time frame: 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

The number of courses needed to achieve complete remission after single-agent chemotherapy in two arms

Time frame: 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)

Incidence and severity of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 in two arms

Time frame: through study completion, an average of 3 year

Effects on menstrual conditions and ovarian function

Effects on menstrual conditions and ovarian function measured by Anti-Mullerian hormone（AMH）

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

Locations

Peking Union Medical College Hospital, Beijing, China

Linked Papers

2025-06-19

Efficacy and safety of biweekly single-dose actinomycin D versus multiday methotrexate in low-risk gestational trophoblastic neoplasia: a prospective multicenter randomized trial

Cure rates for low-risk gestational trophoblastic neoplasia (GTN) are high, but there is no consensus on optimal first-line chemotherapy. Here we evaluated the efficacy and safety of biweekly single-dose actinomycin D (Act-D) versus an 8-day methotrexate (MTX)-folinic acid regimen as first-line single-agent chemotherapy for low-risk GTN. This multicenter, randomized, controlled trial enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-III, low-risk GTN (FIGO 2000 prognostic scores 0-4) across eight centers in China (ClinicalTrials.gov identifier: NCT04562558). Patients were randomized (1 : 1) to Act-D (1.25 mg/m Between 27 September 2020, and 18 June 2024, 228 patients were randomized to MTX or Act-D. Act-D achieved significantly higher single-agent CR rates than MTX (72.8% versus 54.4%, P = 0.0038) with shorter median remission time (7.86 versus 9.43 weeks, P = 0.0296). Overall CR rates were 100% in both groups following combination chemotherapy for resistant cases. Most adverse events were grade 1-2, but grade ≥2 nausea and vomiting and hair loss were more frequent with Act-D, and alanine aminotransferase was more frequently elevated in the MTX group. Anti-Müllerian hormone reductions were transient in both groups. After a 28.5-month median follow-up, recurrence rates remained low and comparable (MTX 0.88% versus Act-D 0.88%; P > 0.05). Fertility outcomes were favorable in both groups. Biweekly Act-D demonstrated superior efficacy and faster remission than the 8-day MTX regimen as first-line single-agent chemotherapy for low-risk GTN, offering a well-tolerated option despite a higher incidence of nausea, vomiting, and hair loss.

Linked Investigators

Beibei Wu

C. Li

Fang Jiang

M. Du

Yang Xiang

Y. Li