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

Phase 3
18 Years
Open (Enrolling)
Gestational Trophoblastic Tumor

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Trial Information

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



- 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.


- To describe the frequency of post protocol surgical treatment for each arm.

- To describe the frequency of post protocol multi-agent chemotherapy treatment for each

- To compare multi-day methotrexate to dactinomycin with respect to frequency and
severity of adverse events in patients with low-risk gestational trophoblastic

- 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.

- To assess whether uterine artery pulsatility index (UAPI) can provide independent
prognostic information predictive of single-drug resistance.

OUTLINE: This is a multicenter study. Patients are stratified by country where treatment is
given, and multi-day methotrexate regimen (5 days vs 8 days). Patients are randomized to 1
of 2 treatment arms.

- Arm I: 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.

- Arm II: Patients receive dactinomycin IV over 15 minutes on day 1. In both arms,
treatment repeats every 14 days for up to 13 courses* in the absence of disease
progression or unacceptable toxicity.

Patients complete the Functional Assessment of Cancer Therapy (FACT-G) surveys at baseline,
during, and after completion of study treatment.

Patients may undergo Doppler ultrasound to measure the left and right uterine artery
pulsatility indices (UAPI) at baseline.

After completion of study treatment, patients are followed up every 3 months for 2 years.

NOTE: * Patients will be treated for three courses after 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; 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 1 criterion
for GTN defined as:

- A < 10% decrease in the human chorionic gonadotropin (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)

- 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)

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

- Choriocarcinoma meeting 1 of the following criteria:

- Histologically proven non-metastatic choriocarcinoma

- 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

- No patients with non-gestational choriocarcinoma

- No patients with placental-site trophoblastic tumor (PSTT) or epithelioid
trophoblastic tumor (ETT)


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

- White blood cell (WBC) ≥ 3,000 cells/mcL

- Granulocytes ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Creatinine ≤ 2.0 mg/dcL

- Bilirubin ≤ 1.5 times institutional normal

- ALT and AST ≤ 3 times institutional normal

- Alkaline phosphatase ≤ 3 times institutional normal

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

- 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

- No patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4

- No patients whose circumstances at the time of study entry do not permit completion
of the study or required follow-up

- No patients who wish to breast-feed during treatment


- No patients who have previously been treated with cytotoxic chemotherapy

- Patients who received prior low-dose methotrexate for treatment of an ectopic
pregnancy will be eligible for this study

- No patients who have received prior pelvic radiation

- Patients are excluded if their previous cancer treatment contraindicates this
protocol therapy

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response vs treatment failure

Safety Issue:


Principal Investigator

Julian C. Schink, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Robert H. Lurie Cancer Center



Study ID:




Start Date:

July 2012

Completion Date:

Related Keywords:

  • Gestational Trophoblastic Tumor
  • gestational trophoblastic tumor
  • hydatidiform mole
  • low risk metastatic gestational trophoblastic tumor
  • uterine choriocarcinoma
  • stage I gestational trophoblastic tumor
  • stage II gestational trophoblastic tumor
  • stage III gestational trophoblastic tumor
  • Neoplasms
  • Trophoblastic Neoplasms
  • Gestational Trophoblastic Neoplasms



University of Chicago Cancer Research CenterChicago, Illinois  60637
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain CampusNew Britain, Connecticut  06050
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical CenterMilwaukee, Wisconsin  53201-2901
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
St. John's Regional Health CenterSpringfield, Missouri  65804
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Cancer Care Associates - Saint Francis CampusTulsa, Oklahoma  74136-1929
Rosenfeld Cancer Center at Abington Memorial HospitalAbington, Pennsylvania  19001
Northeast Georgia Medical CenterGainesville, Georgia  30501
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical CenterGreen Bay, Wisconsin  54311
Fox Chase Cancer Center CCOP Research BasePhiladelphia, Pennsylvania  19140
Gynecologic OncologyHinsdale, Illinois  60521
Aurora Women's Pavilion of West Allis Memorial HospitalWest Allis, Wisconsin  53227
Mercy Clinic Cancer and Hematology - RollaRolla, Missouri  65401