Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia

Study Overview
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Brief Summary
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Randomized phase III trial to compare the effectiveness of methotrexate with that of dactinomycin in treating patients who have gestational trophoblastic neoplasia. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether methotrexate is more effective than dactinomycin in treating patients with gestational trophoblastic neoplasia.

Detailed Description
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OBJECTIVES: I. Compare the efficacy of methotrexate vs dactinomycin, as measured by complete response rate, in patients with low-risk gestational trophoblastic neoplasia. II. Compare the toxicity of these regimens in these patients. III. Determine whether the definition of persistent gestational trophoblastic neoplasia is accurate (as determined by the likelihood that the beta human chorionic gonadotropin [HCG] titer would decline on the day treatment is initiated). OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive methotrexate intramuscularly once weekly in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive dactinomycin IV over 15 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. All patients continue on treatment until 1 beta human chorionic gonadotropin (HCG) titer is below the institutional normal. Patients then receive 1 additional consolidation treatment. Patients are followed every 4 weeks for 1 year.

Official Title
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A Randomized Phase III Trial of Weekly Parenteral Methotrexate Versus Pulsed Dactinomycin as Primary Management for Low Risk Gestational Trophoblastic Neoplasia

Conditions
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Good Prognosis Metastatic Gestational Trophoblastic Tumor, Hydatidiform Mole, Non-Metastatic Gestational Trophoblastic Tumor, Uterine Corpus Choriocarcinoma

Intervention / Treatment
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* Biological: Dactinomycin
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven low-risk gestational trophoblastic neoplasia (persistent hydatidiform mole or choriocarcinoma), defined as 1 of the following: Less than 10% decrease in the beta human chorionic gonadotropin (HCG) titer over 3 weekly titers Greater than 20% sustained rise in beta HCG titer over two consecutive weeks Persistently elevated beta HCG titer more than 4 months after initial curettage (greater than 5 mIU/mL minimum) Histologically proven nonmetastatic choriocarcinoma Metastases to vagina, parametria, or lung (if no single pulmonary lesion is greater than 2 cm) WHO score 0-6 (not including blood group or CT lung) No histologically confirmed placental site pseudotumor Must have undergone at least 1 uterine curettage Previously untreated disease Performance status - GOG 0-2 WBC at least 3,000/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGPT and SGOT no greater than 3 times ULN Alkaline phosphatase no greater than 3 times ULN No significant prior abnormal hepatic function Creatinine no greater than 2.0 mg/dL No significant prior abnormal renal function Not pregnant or nursing Fertile patients must use effective contraception during and for one year after study entry No other prior or concurrent malignancies within the past 5 years except nonmelanomatous skin cancer No prior chemotherapy for gestational trophoblastic neoplasia No concurrent curettage except as needed to control vaginal bleeding or to rule out placental site pseudotumor
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: Arm I (methotrexate)<br>Patients receive methotrexate intramuscularly once weekly in the absence of disease progression or unacceptable toxicity. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive 1 additional consolidation treatment. | Drug: Methotrexate<br>* Given intramuscularly<br>* Other names: WR-19039;|
| Experimental: Arm II (dactinomycin)<br>Patients receive dactinomycin IV over 15 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive 1 additional consolidation treatment. | Biological: Dactinomycin<br>* Given IV<br>* Other names: Meractinomycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Primary outcome is measured as a difference in proportion responding between treatment arms and evaluated using a chi square test. A complete response was defined as a normal hCG sustained over four weekly measurements. | Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months. | 
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 | Number of participants with a maximum grade of 3 or higher during the treatment period. | Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With a Decline of hCG on Day 1 of Treatment | Number of patients with a decline in hCG on day 1 of treatment relative to the level at enrollment. A decline is defined as a decrease by 1 or more units between enrollment and treatment start. | Prior to study entry and on Day 1 of treatment |