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

Phase 3

Completed

Conditions: Choriocarcinoma
FIGO Stage I Gestational Trophoblastic Tumor
FIGO Stage II Gestational Trophoblastic Tumor
FIGO Stage III Gestational Trophoblastic Tumor
Hydatidiform Mole

Interventions: Biological: Dactinomycin
Drug: Leucovorin Calcium
Other: Quality-of-Life Assessment
Drug: Methotrexate

Registration Number: NCT01535053

Lead Sponsor: GOG Foundation

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (dactinomcin)	Dactinomycin	Patients receive dactinomycin IV over 15 minutes on day 1.
Arm I (dactinomcin)	Quality-of-Life Assessment	Patients receive dactinomycin IV over 15 minutes on day 1.
Arm II (leucovorin calcium and methotrexate)	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.
Arm II (leucovorin calcium and methotrexate)	Quality-of-Life Assessment	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.
Arm II (leucovorin calcium and methotrexate)	Leucovorin Calcium	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Response	hCG testing is performed prior to each cycle to treatment until treatment is completed, up to 10 months. For patients who have responded to treatment hCG must be obtained every 4 weeks for 1 year after completing treatment.	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With CTCAE v4 Graded Adverse Events With Low-risk Gestational Trophoblastic Neoplasia by Arm	Assessed throughout the treatment period and within 2-4 weeks after discontinuation of treatment	Maximum grade of physician assessed adverse events reported during treatment
The Number of Participants With Post Protocol Surgical Treatment for Each Arm.	Anytime during post treatment follow-up for up to 2 years from study entry.
The Number of Participants With Post Protocol Multi-agent Chemotherapy Treatment for Each Arm.	Anytime during post treatment follow-up for up to 2 years from study entry.
Patient-reported Quality of Life (QOL) at Baseline	Prior to cycle 1	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.
Patient-reported Quality of Life (QOL) After Baseline Visit.	Prior to cycle 3 (4 weeks after cycle 1 if off study treatment prior to cycle 3). Prior to cycle 5, Prior to cycle 7, 26 weeks after starting study 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.

Trial Locations

Locations (289): Anchorage Associates in Radiation Medicine
🇺🇸
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸
Anchorage, Alaska, United States
Alaska Regional Hospital
🇺🇸
Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸
Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸
Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸
Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Cancer Center at Saint Joseph's
🇺🇸
Phoenix, Arizona, United States
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Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States