A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia
A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia
This randomized phase III trial studies how well methotrexate works compared to dactinomycin in treating patients with low-risk gestational trophoblastic neoplasia. Drugs used in chemotherapy, such as methotrexate and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether methotrexate is more effective than dactinomycin in treating gestational trophoblastic disease.
PRIMARY OBJECTIVES:
I. To test the hypothesis that treatment with multi-day methotrexate is inferior to treatment with pulse actinomycin-D (dactinomycin) in patients with low-risk gestational trophoblastic disease with respect to complete response.
SECONDARY OBJECTIVES:
I. To describe the frequency of post protocol surgical treatment for each arm. II. To describe the frequency of post protocol multi-agent chemotherapy treatment for each arm.
III. To compare multi-day methotrexate to actinomycin-D with respect to frequency and severity of adverse events in patients with low-risk gestational trophoblastic neoplasia.
IV. To investigate the impact of treatment on overall quality-of-life (QOL) and explore the influence of treatment on issues such as body image, sexual functioning, and patient-reported side effects and disruption.
V. To assess whether uterine artery pulsatility index (UAPI) can provide independent prognostic information predictive of single-drug resistance.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive dactinomycin intravenously (IV) over 15 minutes on day 1.
ARM II: Patients receive methotrexate intramuscularly (IM) on days 1, 3, 5, and 7 and leucovorin calcium orally (PO) on days 2, 4, 6, and 8 OR single agent methotrexate IV on days 1-5.
In both arms, treatment repeats every 14 days for up to 20 courses* in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year and then every 3 months for 1 year.
NOTE: * Patients will be treated for three courses after human chorionic gonadotropin (hCG) < 5 mIU/mL or until evidence of treatment failure (biologic progression), disease progression, or unacceptable toxicity despite dose modifications. Upon normalization of hCG (< 5 mIU/mL), patients will be treated with three additional courses.
Inclusion Criteria:
Patients who meet International Federation of Gynecology and Obstetrics (FIGO) stage I, II, or III 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:
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:
Choriocarcinoma
World Health Organization (WHO) risk score 0-6
Patients must be willing to practice effective contraception for the duration of the study
White blood cell count (WBC) >= 3,000 cells/mcL
Granulocytes >= 1,500/mcL
Platelets >= 100,000/mcL
Creatinine =< 2.0 mg/dcL
Bilirubin =< 1.5 x institutional normal
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x institutional normal
Alkaline phosphatase =< 3 x institutional normal
Patients who have met the pre-entry requirements
Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Exclusion Criteria:
Burbank, California 91505, United States
Highland Park, Illinois 60035, United States
Saint Louis Park, Minnesota 55416, United States
Spokane, Washington 99204, United States
Spokane, Washington 99218, United States
Spokane Valley, Washington 99216, United States
Yakima, Washington 98902, United States
Summit, Wisconsin 53066, United States
Shiwa-gun, Iwate 028-3695, Japan
Nakagami-gun, Okinawa 903-0215, Japan