Clinical trial NCT00003702: Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia
Official title: A Randomized Phase III Trial of Weekly Parenteral Methotrexate Versus "Pulsed" Dactinomycin as Primary Management for Low Risk Gestational Trophoblastic Neoplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Good Prognosis Metastatic Gestational Trophoblastic Tumor
Hydatidiform Mole
Non-Metastatic Gestational Trophoblastic Tumor
Uterine Corpus Choriocarcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: Eastern Cooperative Oncology Group
name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 240
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay
timeFrame: Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months.
measure: Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
timeFrame: Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months.
Secondary outcomes:
measure: Number of Patients With a Decline of hCG on Day 1 of Treatment
timeFrame: Prior to study entry and on Day 1 of treatment
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Raymond Osborne
role: PRINCIPAL_INVESTIGATOR
References: