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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gestational Trophoblastic Tumor, Gestational Trophoblastic Neoplasia, Stage I Gestational Trophoblastic Tumor, Stage II Gestational Trophoblastic Tumor, Stage III Gestational Trophoblastic Tumor, Invasive Mole, Choriocarcinoma

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Leucovorin
* Drug: Dactinomycin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective，multicenter，randomized trial with two arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1-Methotrexate<br>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<br>* 50mg intramuscularly on Days 1, 3, 5, 7 . Repeat every 14 days<br>* Other names: MTX;Drug: Leucovorin<br>* 15mg intramuscularly on Days 2, 4, 6, 8. Repeat every 14 days<br>* Other names: Calcium folinate;|
| Experimental: Arm 2-Dactinomycin<br>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<br>* 1.25mg/m2 (2mg max dose)intravenous every 14 days.<br>* Other names: dactinomycin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration needed to achieve complete remission after single-agent chemotherapy | The duration needed to achieve complete remission after single-agent in two arms | 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 | 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 | 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） | Prior to treatment begin，and 6 month after single-agent chemotherapy completion, an average of 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gestational trophoblastic neoplasia, actinomycin-D, methotrexate, low-risk