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

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Annette Paulsen

Principal Investigator
David Miller, M.D.

Official Title

A Phase III Randomized Trial of Pulse Actinomycin-D Versus Multi-day Methotrexate for the Treatment of Low-Risk Gestational Trophoblastic Neoplasia

Brief Overview

This randomized phase III trial studies how well methotrexate works compared to dactinomycin
in treating patients with low-risk gestational trophoblastic neoplasia. 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, by stopping them from dividing, or by
stopping them from spreading. It is not yet known whether methotrexate is more effective
than dactinomycin in treating gestational trophoblastic disease.



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.

Participant Eligibility

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

- World Health Organization (WHO) risk score 0-6

- Patients must be willing to practice effective contraception for the duration of the

- 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