Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

Study Overview
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Brief Summary
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The investigators conducted a trial to determine whether methotrexate or methotrexate/dactinomycin single-course treatment work well as multiple courses of single methotrexate chemotherapy in low-risk gestational trophoblastic neoplasia. It is not yet known whether single-course of chemotherapy is as the same effectiveness as multicourse.

Official Title
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A Multicenter, Prospective, Randomized Trial of Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

Conditions
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Gestational Trophoblastic Disease, Gestational Trophoblastic Neoplasia, Gestational Trophoblastic Tumor, Gestational Trophoblastic Neoplasms

Intervention / Treatment
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* Drug: MTX 1
* Drug: MTX 2
* Biological: Act-d


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who FIGO Stage I, II, or III criteria for low-risk gestational trophoblastic neoplasia (GTN); WHO risk score 0-6; Age≤60 years; female, Chinese women; Initial treatment is chemotherapy; patients who received prior low-dose methotrexate for treatment of an ectopic pregnancy will be eligible for this study; Performance status: Karnofsky score≥60; Laboratory tests: WBC≥3.5×10(9)/L, ANC≥1.5×10(9)/L, PLT≥80×10(9)/L, serum bilirubin≤ 1.5 times the upper limit of normal, transaminase≤ 1.5 times the upper limit of normal, BUN, Cr≤ normal Provide written informed consent. Exclusion Criteria: Patients with unconfirmed diagnosis of GTN; Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) WHO risk score >6; 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: 60 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methotrexate Single-coure chemotherapy<br>Regimen: Methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5. If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen. | Drug: MTX 1<br>* MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5<br>|
| Experimental: Methotrexate+dactinomycin Single-dose chemotherapy<br>Regimen: dactinomycin d 0.6mg/m2, IV, on day1, 2; methotrexate 100mg/m2, IV, on day1 (after Act-d); methotrexate 200mg/m2, IVgtt, on day1 (after methotrexate, 500ml NS, >4h). If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen. | Drug: MTX 2<br>* MTX 100mg/m(2), IV, on day1 (after Act-d); MTX 200mg/m(2), IVgtt, on day1 (after MTX, 500ml NS, >4h)<br>Biological: Act-d<br>* Act-d 0.6mg/m(2), IV, on day1,2<br>|
| Active Comparator: MTX multiple courses chemotherapy<br>Regimen: methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5, 2-week intervals. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive at least 1 additional consolidation treatment. After treatment, all the patients were asked for contraception with condom or oral contraception. Regular hCG surveillance, once a month for 3 consecutive months and once every 3 months for 2 years, was performed. During follow-up period, pelvic ultrasound and pulmonary X ray or CT scan were conducted if needed. | Drug: MTX 1<br>* MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) by single-course |  | through study completion, an average of 1 year | 
| Completely remission rate by multiple courses after single-course failure |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| remission rate of ACTD replacement after MTX resistance |  | through study completion, an average of 1 year | 
| the number of courses needed to achieve complete remission after multi-course treatment |  | through study completion, an average of 1 year | 
| complete remission rate by multidrug combination therapy after single drug failure |  | through study completion, an average of 1 year |