Good Prognosis Metastatic Gestational Trophoblastic Tumor, Hydatidiform Mole, Non-Metastatic Gestational Trophoblastic Tumor, Uterine Corpus Choriocarcinoma
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALDactinomycin
Given IV
DRUGMethotrexate
Given intramuscularly
Sponsors
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months. | 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. |
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 | Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months. | Number of participants with a maximum grade of 3 or higher during the treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With a Decline of hCG on Day 1 of Treatment | Prior to study entry and 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. |
Countries
United States
Participant flow
Recruitment details
This trial opened to patient accrual on 6/14/1999 and closed to accrual on 2/26/2007.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly Arm 1: Methotrexate 30 mg/m2 IM weekly | 107 |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks | 109 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not meet criteria for persistence | 8 | 5 |
| Overall Study | Inadequate documentation of disease | 1 | 3 |
| Overall Study | Ineligible cell types | 2 | 2 |
| Overall Study | WHO score > 6 | 2 | 1 |
Baseline characteristics
| Characteristic | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 28.8 years STANDARD_DEVIATION 7.9 | 30.4 years STANDARD_DEVIATION 8.6 | 29.6 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 107 Participants | 109 Participants | 216 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 107 | 68 / 107 |
| serious Total, serious adverse events | 0 / 107 | 1 / 107 |
Outcome results
Primary
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.
Time frame: Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months.
Population: Eligible and treated patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 | 14 Participants |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 | 20 Participants |
Primary
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.
Time frame: Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months.
Population: Eligible patients who received a random treatment allocation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Complete/Cure | 57 Participants |
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Non-response | 48 Participants |
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Inevaluable | 2 Participants |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Complete/Cure | 76 Participants |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Non-response | 29 Participants |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay | Inevaluable | 4 Participants |
Secondary
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.
Time frame: Prior to study entry and on Day 1 of treatment
Population: Eligible and evaluated patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | Number of Patients With a Decline of hCG on Day 1 of Treatment | 72 Participants |