Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia

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:

- A < 10% decrease in the hCG level using as a reference the first value
in the series of 4 values taken over a period of 3 weeks (> 50 mIU/ml
minimum) OR

- A > 20% sustained rise in the hCG taking as a reference the first value
in the series of 3 values taken over a period of 2 weeks (> 50 mIU/ml
minimum) OR

- A persistently elevated hCG level a period of 6 months or more
following the initial curettage (> 50 mIU/ml minimum)

- Choriocarcinoma

- Histologically proven non-metastatic choriocarcinoma OR

- Histologically proven metastatic choriocarcinoma if the metastatic site(s)
is restricted to one (or more) of the following: vagina, parametrium, or
lung

- 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:

- Patients who do not have GTN

- Patients with non-gestational choriocarcinoma

- Patients who have previously been treated with cytotoxic chemotherapy; however,
patients who received prior low-dose methotrexate for treatment of an ectopic
pregnancy will be eligible for this study

- Patients who have received prior pelvic radiation

- Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic
tumor (ETT)

- Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last five years; patients are also excluded if their previous
cancer treatment contraindicates this protocol therapy

- Patients whose circumstances at the time of study entry do not permit completion of
the study or required follow-up

- Patients who wish to breast-feed during treatment