Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia - Full Text View

Sponsor:	Gynecologic Oncology Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003702

Purpose

RATIONALE: 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.

PURPOSE: Randomized phase III trial to compare the effectiveness of methotrexate with that of dactinomycin in treating patients who have gestational trophoblastic neoplasia.

Condition	Intervention	Phase
Gestational Trophoblastic Tumor	Biological: dactinomycin Drug: methotrexate	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	A Randomized Trial of Weekly Parenteral Methotrexate Versus "Pulsed" Dactinomycin as Primary Manangement for Low Risk Gestational Trophoblastic Neoplasia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cancer and Pregnancy

Drug Information available for: Dactinomycin Methotrexate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Frequency of objective (complete) response as measured by normal beta human chorionic gonadotropin (HCG) levels [ Designated as safety issue: No ]
Frequency and severity of observed adverse effects [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Cure rate as measured by normal beta HCG levels [ Designated as safety issue: No ]

Estimated Enrollment:	216
Study Start Date:	June 1999
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive methotrexate intramuscularly once weekly in the absence of disease progression or unacceptable toxicity. Patients continue on treatment until 1 beta human chorionic gonadotropin (HCG) titer is below the institutional normal. Patients then receive 1 additional consolidation treatment.	Drug: methotrexate Given intramuscularly
Experimental: Arm II 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

Detailed Description:

OBJECTIVES:

Compare the efficacy of methotrexate vs dactinomycin, as measured by complete response rate, in patients with low-risk gestational trophoblastic neoplasia.
Compare the toxicity of these regimens in these patients.
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.

PROJECTED ACCRUAL: A total of 216 patients will be accrued for this study within 4 years.

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

GOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

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

Renal:

Creatinine no greater than 2.0 mg/dL
No significant prior abnormal renal function

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy for gestational trophoblastic neoplasia

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

See Disease Characteristics
No concurrent curettage except as needed to control vaginal bleeding or to rule out placental site pseudotumor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003702

Show 66 Study Locations

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Investigators

Study Chair:	Raymond Osborne, MD, FRCSC, MBA	Odette Cancer Centre at Sunnybrook
Study Chair:	Higinia R. Cardenes, MD, PhD	Indiana University Melvin and Bren Simon Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, Provencher D, Miller DS, Covens AL, Lage JM. Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study. J Clin Oncol. 2011 Jan 24; [Epub ahead of print]

ClinicalTrials.gov Identifier:	NCT00003702 History of Changes
Other Study ID Numbers:	CDR0000066809, GOG-174, ECOG-G174
Study First Received:	November 1, 1999
Last Updated:	January 7, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

hydatidiform mole
uterine choriocarcinoma
nonmetastatic gestational trophoblastic tumor
low risk metastatic gestational trophoblastic tumor

Additional relevant MeSH terms:

Trophoblastic Neoplasms
Gestational Trophoblastic Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Pregnancy Complications, Neoplastic
Pregnancy Complications
Dactinomycin
Methotrexate
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on February 09, 2012