Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia
|ClinicalTrials.gov Identifier: NCT01535053|
Recruitment Status : Active, not recruiting
First Posted : February 17, 2012
Last Update Posted : August 24, 2017
|Condition or disease||Intervention/treatment||Phase|
|Choriocarcinoma FIGO Stage I Gestational Trophoblastic Tumor FIGO Stage II Gestational Trophoblastic Tumor FIGO Stage III Gestational Trophoblastic Tumor Hydatidiform Mole||Biological: Dactinomycin Drug: Leucovorin Calcium Drug: Methotrexate Other: Quality-of-Life Assessment||Phase 3|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||384 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia|
|Actual Study Start Date :||June 18, 2012|
|Estimated Primary Completion Date :||May 31, 2018|
Experimental: Arm I (dactinomcin)
Patients receive dactinomycin IV over 15 minutes on day 1.
Given IVOther: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Active Comparator: Arm II (leucovorin calcium and methotrexate)
Patients receive methotrexate IM on days 1, 3, 5, and 7 and leucovorin calcium PO on days 2, 4, 6, and 8 OR single agent methotrexate IV on days 1-5.
Drug: Leucovorin Calcium
Given PODrug: Methotrexate
Given IV and IMOther: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Complete response vs treatment failure [ Time Frame: Up to 2 years ]The information fraction is estimated by the number of eligible patients evaluated for response at a given time divided by the target sample size of eligible patients. However, the timing of the interim analyses will likely vary from this exact schedule for practical reasons. At the interim analysis, the test statistic for the primary analysis will be compared with the critical boundaries defined by the statistical design parameters an O'Brien and Fleming alpha spending function as proposed by Lan and DeMets.
- Overall QOL as measured by Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: Up to 26 weeks ]A linear mixed model that accounts for the correlation among the repeated measures will be fitted for the FACT-G score adjusting for baseline score and other covariates. The patient-reported symptom measurement scores and treatment disruption on QOL will be summarized by treatment arms with the estimated means for continuous variables or frequency tables for categorical variables accompanied with 95% confidence intervals.
- Severity of adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 2 years ]The maximum grade of any adverse event observed during active treatment period or within 4 weeks of completing study treatment for each eligible patient will be tabulated. The proportion of patients with a serious adverse event or reported grade 3 or worse adverse event, regardless of attribution, will be compared between the treatment regimens using a chi-square test.
- UAPI (optional) [ Time Frame: Up to 2 years ]Analyses will report predictiveness curves (with observed risk for assessing calibration) for UAPI with and without the interaction term, functions of sensitivity, specificity and risk, risk distribution by treatment outcome, and area under curve from receiver operating characteristic analysis. These analyses will help to evaluate the predictive accuracy of UAPI when predicting resistance to standard single agent therapy.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01535053
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|Principal Investigator:||Julian Schink||NRG Oncology|