Study Design and Treatment Randomization: This study is designed as a two arm randomized phase iii non-inferiority trial with a control arm using actinomycin-D (aCT-D) and an experimental arm using one of two multi-day methotrexate (MTX) regimen chosen by the participating site. The design will provide a direct assessment of
the null hypothesis that the efficacy attributed to multi-day methotrexate regimens is inferior to that of aCT -D given every two weeks. each iRB-approved participating site will declare upfront which MTX regimen they will use for the duration of the trial.
Prior to patient registration, eligibility will be reviewed by FFS verification. The sequence of treatment assignments will be concealed from institutions and patients until registration with verification of eligibility. Patients will be registered by the participating site through oPen and randomization will be carried out centrally by the GoG Statistical and Data Center. The randomization will be stratified by the country (a surrogate for health care system) where treatment is given and the multi-day methotrexate regimen to be used by the institution using a minimization procedure that tends to allocate two study arms in a ratio of 1 to 1 within strata.
eligible, consented patients will be randomized to one of the following two
Regimen 1: Patients will receive iV pulse actinomycin-D (1.25 mg/m2) once
every 14 days. Maximum dose is 2 mg.
Regimen 2: Patients will receive their institutional preference of either iV
methotrexate (0.4mg/kg) daily for 5 days every 14 days with a maximum daily
dose of 25 mg.
iM methotrexate (50mg) on Days 1,3,5,7 (4 doses per cycle) with Leucovorin
(15mg) orally on Days 2, 4, 6, 8 within 24-30 hours of the preceding day's
injection. Repeated every 14 days.
Patients receiving iM methotrexate will be instructed to take Leucovorin Po between 24 -30 hours after the preceding injection. if a patient misses a dose of Leucovorin she should be instructed to take the pill as soon as she remembers unless it is within 12 hours of the next scheduled methotrexate dose. if it is 12 hours or closer to the next iM methotrexate injection, the patient should be instructed to skip that dose.
3.11 Patients who meet F.I.G.O. Stage I, II, or III criteria (See Appendix I-F.I.G.O. Staging Criteria) for low-risk gestational trophoblastic neoplasia (GTN): post molar GTN or choriocarcinoma (as defined below). Patients may have had a second curettage but must still meet GTN criteria below.
3.111 Post Molar GTN
For the purposes of this study, patients must have undergone evacuation of a complete or partial hydatidiform mole and then meet the criteria for GTN defined as:
3.1111 A < 10% decrease in the hCG level using as a reference the first value in the series of 4 values taken over a period of 3weeks (>50 mIU/ml minimum).
3.1112 A > 20% sustained rise in the hCG taking as a reference the first value in the series of 3 values taken over a period of 2weeks (>50 mIU/ml minimum).
3.1113 A persistently elevated hCG level a period of 6 months or more following the initial curettage (>50 mIU/ml minimum).
3.1121 Histologically proven non-metastatic choriocarcinoma.
3.1122 Histologically proven metastatic choriocarcinoma if the metastatic
site(s) is restricted to one (or more) of the following: vagina,
parametrium, or lung.
3.12 W.H.O. risk score 0-6 (See Appendix II-W.H.O. Risk Scoring Criteria).
3.13 Patients must be willing to practice effective contraception for the duration of the study.
3.14 Patients must have normal hepatic, hematologic, and renal function:
WBC >= 3,000 cells/mcl;
Granulocytes >= 1500/mcl;
Platelets >= 100,000/mcl;
Creatinine <= 2.0 mg/dcl;
Bilirubin <= 1.5x institutional normal;
ALT, AST and alkaline phosphatase <= 3x institutional normal.
Patients who have met the pre-entry requirements specified in Section 7.0.
Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy.
3.17 Patients must have signed an approved informed consent and authorization permitting release of personal health information.
3.18 Patients must be 18 years of age and older.