Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia

April 12, 2018 updated by: Gynecologic Oncology Group

A Randomized Phase III Trial of Weekly Parenteral Methotrexate Versus "Pulsed" Dactinomycin as Primary Management for Low Risk Gestational Trophoblastic Neoplasia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19103
        • Gynecologic Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I (methotrexate)
Patients receive methotrexate intramuscularly once weekly in the absence of disease progression or unacceptable toxicity. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive 1 additional consolidation treatment.
Drug: Methotrexate
Given intramuscularly
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
EXPERIMENTAL: Arm II (dactinomycin)
Patients receive dactinomycin IV over 15 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive 1 additional consolidation treatment.
Biological: Dactinomycin
Given IV
Other Names:
  • Cosmegen
  • Actinomycin A IV
  • Actinomycin C1
  • ACTINOMYCIN D
  • Actinomycin I1
  • Actinomycin IV
  • Actinomycin X 1
  • Actinomycin-[thr-val-pro-sar-meval]
  • DACT
  • Dactinomycine
  • Lyovac Cosmegen
  • Meractinomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay
Time Frame: 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.
Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
Time Frame: 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.
Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With a Decline of hCG on Day 1 of Treatment
Time Frame: 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.
Prior to study entry and on Day 1 of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gynecologic Oncology Group

Collaborators

National Cancer Institute (NCI)
Eastern Cooperative Oncology Group

Investigators

  • Principal Investigator: Raymond Osborne, Gynecologic Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1999

Primary Completion (ACTUAL)

July 1, 2010

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ACTUAL)

May 15, 2018

Last Update Submitted That Met QC Criteria

April 12, 2018

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOG-0174 (OTHER: CTEP)
  • U10CA027469 (U.S. NIH Grant/Contract)
  • NCI-2011-02026 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • ECOG-G174
  • CDR0000066809

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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