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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Gynecologic Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01535053
First received: February 14, 2012
Last updated: July 13, 2015
Last verified: July 2015

February 14, 2012
July 13, 2015
June 2012
August 2016   (final data collection date for primary outcome measure)
Complete response vs treatment failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
The information fraction is estimated by the number of eligible patients evaluated for response at a given time divided by the target sample size of eligible patients. However, the timing of the interim analyses will likely vary from this exact schedule for practical reasons. At the interim analysis, the test statistic for the primary analysis will be compared with the critical boundaries defined by the statistical design parameters an O'Brien and Fleming alpha spending function as proposed by Lan and DeMets.
Complete response [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01535053 on ClinicalTrials.gov Archive Site
  • Overall QOL as measured by Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
    A linear mixed model that accounts for the correlation among the repeated measures will be fitted for the FACT-G score adjusting for baseline score and other covariates. The patient-reported symptom measurement scores and treatment disruption on QOL will be summarized by treatment arms with the estimated means for continuous variables or frequency tables for categorical variables accompanied with 95% confidence intervals.
  • Severity of adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The maximum grade of any adverse event observed during active treatment period or within 4 weeks of completing study treatment for each eligible patient will be tabulated. The proportion of patients with a serious adverse event or reported grade 3 or worse adverse event, regardless of attribution, will be compared between the treatment regimens using a chi-square test.
  • UAPI (optional) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Analyses will report predictiveness curves (with observed risk for assessing calibration) for UAPI with and without the interaction term, functions of sensitivity, specificity and risk, risk distribution by treatment outcome, and area under curve from receiver operating characteristic analysis. These analyses will help to evaluate the predictive accuracy of UAPI when predicting resistance to standard single agent therapy.
  • Severity of adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4 [ Designated as safety issue: Yes ]
  • Overall QOL [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Choriocarcinoma
  • FIGO Stage I Gestational Trophoblastic Tumor
  • FIGO Stage II Gestational Trophoblastic Tumor
  • FIGO Stage III Gestational Trophoblastic Tumor
  • Hydatidiform Mole
  • Biological: Dactinomycin
    Given IV
    Other Names:
    • Actinomycin A IV
    • Actinomycin C1
    • ACTINOMYCIN D
    • Actinomycin I1
    • Actinomycin IV
    • Actinomycin X 1
    • Actinomycin-[thr-val-pro-sar-meval]
    • Cosmegen
    • DACT
    • DACTINOMYCIN
    • Dactinomycine
    • Lyovac Cosmegen
    • Meractinomycin
  • Drug: Leucovorin Calcium
    Given PO
    Other Names:
    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • Citrovorum Factor
    • Cromatonbic Folinico
    • Dalisol
    • Disintox
    • Divical
    • Ecofol
    • Emovis
    • Factor, Citrovorum
    • Flynoken A
    • Folaren
    • Folaxin
    • FOLI-cell
    • Foliben
    • Folidan
    • Folidar
    • Folinac
    • Folinate Calcium
    • folinic acid
    • Folinic Acid Calcium Salt Pentahydrate
    • Folinoral
    • Folinvit
    • Foliplus
    • Folix
    • Imo
    • Lederfolat
    • Lederfolin
    • Leucosar
    • leucovorin
    • LEUCOVORIN CALCIUM
    • Rescufolin
    • Rescuvolin
    • Tonofolin
    • Wellcovorin
  • Drug: Methotrexate
    Given IV and IM
    Other Names:
    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS
    • Lantarel
    • Ledertrexate
    • Lumexon
    • Maxtrex
    • Medsatrexate
    • Metex
    • Methoblastin
    • METHOTREXATE
    • Methotrexate LPF
    • Methotrexate Methylaminopterin
    • Methotrexatum
    • Metotrexato
    • Metrotex
    • Mexate
    • Mexate-AQ
    • MTX
    • Novatrex
    • Rheumatrex
    • Texate
    • Tremetex
    • Trexeron
    • Trixilem
    • WR-19039
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Experimental: Arm I (dactinomcin)
    Patients receive dactinomycin IV over 15 minutes on day 1.
    Interventions:
    • Biological: Dactinomycin
    • Other: Quality-of-Life Assessment
  • Active Comparator: Arm II (leucovorin calcium and methotrexate)
    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.
    Interventions:
    • Drug: Leucovorin Calcium
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
384
Not Provided
August 2016   (final data collection date for primary outcome measure)

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 (as defined below); 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 the criteria for GTN defined as:

        • A < 10% decrease in the 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) OR
        • 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) OR
        • A persistently elevated hCG level a period of 6 months or more following the initial curettage (> 50 mIU/ml minimum)
    • Choriocarcinoma

      • Histologically proven non-metastatic choriocarcinoma OR
      • Histologically proven metastatic choriocarcinoma if the metastatic site(s) is restricted to one (or more) of the following: vagina, parametrium, or lung
  • World Health Organization (WHO) risk score 0-6
  • Patients must be willing to practice effective contraception for the duration of the study
  • White blood cell count (WBC) >= 3,000 cells/mcL
  • Granulocytes >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Creatinine =< 2.0 mg/dcL
  • Bilirubin =< 1.5 x institutional normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x institutional normal
  • Alkaline phosphatase =< 3 x institutional normal
  • Patients who have met the pre-entry requirements
  • Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Patients who do not have GTN
  • Patients with non-gestational choriocarcinoma
  • Patients who have previously been treated with cytotoxic chemotherapy; however, patients who received prior low-dose methotrexate for treatment of an ectopic pregnancy will be eligible for this study
  • Patients who have received prior pelvic radiation
  • Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)
  • Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4
  • 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; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients whose circumstances at the time of study entry do not permit completion of the study or required follow-up
  • Patients who wish to breast-feed during treatment
Female
18 Years and older
No
United States,   Canada,   Japan,   Korea, Republic of,   United Kingdom
 
NCT01535053
GOG-0275, NCI-2012-00250, CDR0000725211, PGOG-0275_A08PAMDREVW01, GOG-0275, GOG-0275, U10CA180868, U10CA027469
Yes
Gynecologic Oncology Group
Gynecologic Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Julian Schink NRG Oncology
Gynecologic Oncology Group
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP