Methotrexate or Dactinomycin in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia
RATIONALE: 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 or by stopping them from dividing. It is not yet known whether methotrexate is more effective than dactinomycin in treating gestational trophoblastic disease.
PURPOSE: This randomized phase III trial studies how well methotrexate works compared to dactinomycin in treating patients with low-risk gestational trophoblastic neoplasia.
Gestational Trophoblastic Tumor
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-Day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia|
- Complete response vs treatment failure [ Designated as safety issue: No ]
- Severity of adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4 [ Designated as safety issue: Yes ]
- Overall QOL [ Designated as safety issue: No ]
- Factors to be tested for association with treatment failure: WHO risk score, choriocarcinoma histology, uterine artery pulsatility index [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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.
Given IV or IM
Active Comparator: Arm II
Patients receive dactinomycin IV over 15 minutes on day 1.
- 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.
- To describe the frequency of post protocol surgical treatment for each arm.
- To describe the frequency of post protocol multi-agent chemotherapy treatment for each arm.
- To compare multi-day methotrexate to dactinomycin with respect to frequency and severity of adverse events in patients with low-risk gestational trophoblastic neoplasia.
- 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.
- To assess whether uterine artery pulsatility index (UAPI) can provide independent prognostic information predictive of single-drug resistance.
OUTLINE: This is a multicenter study. Patients are stratified by country where treatment is given, and multi-day methotrexate regimen (5 days vs 8 days). Patients are randomized to 1 of 2 treatment arms.
- Arm I: 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.
- Arm II: Patients receive dactinomycin IV over 15 minutes on day 1. In both arms, treatment repeats every 14 days for up to 13 courses* in the absence of disease progression or unacceptable toxicity.
Patients complete the Functional Assessment of Cancer Therapy (FACT-G) surveys at baseline, during, and after completion of study treatment.
Patients may undergo Doppler ultrasound to measure the left and right uterine artery pulsatility indices (UAPI) at baseline.
After completion of study treatment, patients are followed up every 3 months for 2 years.
NOTE: * Patients will be treated for three courses after 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.