Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Trophoblastic Neoplasms

Hydatidiform Mole

Choriocarcinoma

Nevus

Gestational Trophoblastic Disease

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Gestational Trophoblastic Tumor

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Anti-Infective Agents

Bone Density Conservation Agents

Vitamins

Leucovorin

Levoleucovorin

Methotrexate

Calcium

Folic Acid

Dactinomycin

Calcium, Dietary

Cactinomycin

Vitamin B Complex

Hormones

Antimetabolites

Enzyme Inhibitors

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Trace Elements

Anti-Bacterial Agents

Antibiotics, Antitubercular

Folinic Acid

Folate

Vitamin B9

Patients receive dactinomycin IV over 15 minutes on day 1.

Patients receive methotrexate IM on days 1, 3, 5, and 7 and leucovorin calcium PO on days 2, 4, 6, and 8 OR single agent methotrexate IV on days 1-5.

Leucovorin Calcium

Quality-of-Life Assessment

Julian C Schink

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.

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.

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

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

Complete Response is defined as 3 consecutive bi-weekly values of hCG\<5 over a minimum of 4 weeks of normal hCG values with no values greater than 5 mIU/ml

Maximum grade of physician assessed adverse events reported during treatment

Patient reported quality of life was measured with the Functional Assessment of Cancer Therapy - Generic (FACT-G). The FACT-G is a scale for assessing general QOL of cancer patients. It consists of four subscales: Physical Well Being, Functional Well Being, Social/Family Well-Being, and Emotional Well-Being. Each item in the FACT-G was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements, reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-G score is calculated as the sum of the subscale scores. The FACT-G score ranges 0-108. A larger score suggests better QOL.

National Cancer Institute (NCI)

GOG Foundation

Participants listed in the all-cause mortality include all enrolled. Participants in the Serious Adverse Event and Other Adverse Events include all eligible AND treated. Therefore, the number of participants listed in the all-cause mortality is larger than the serious adverse event and other adverse event tables.

IV pulse actinomycin-D (1.25mg/m2 ) every 14 days. (2mg max dose)

Regimen I (Dactinomycin)

institutional preference of either:

* IV methotrexate (0.4 mg/kg) daily for 5 days every 14 days. (25mg max daily dose) OR
* IM methotrexate (50mg) on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days.

Regimen II (Methotrexate)

Total

10-19 years

20-29 years

30-39 years

40-49 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Early closure leading to non-compliance and small numbers of subjects analyzed. Study cannot be considered terminated because some participants are still being examined for follow-up.

Linda Gedeon for Virginia Filiaci, PhD.

Percentage of Participants With Complete Response

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Number of Participants With CTCAE v4 Graded Adverse Events With Low-risk Gestational Trophoblastic Neoplasia by Arm

Non-responding eligible patients in follow-up

The Number of Participants With Post Protocol Surgical Treatment for Each Arm.

The Number of Participants With Post Protocol Multi-agent Chemotherapy Treatment for Each Arm.

Spots Global Cancer Trial Database for figo stage i gestational trophoblastic tumor