Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia (GTN-01)

A Multicenter, Prospective, Randomized Trial of Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

The investigators conducted a trial to determine whether methotrexate or methotrexate/dactinomycin single-course treatment work well as multiple courses of single methotrexate chemotherapy in low-risk gestational trophoblastic neoplasia. It is not yet known whether single-course of chemotherapy is as the same effectiveness as multicourse.

Study Overview

• Status: Unknown
• Conditions: Gestational Trophoblastic Tumor; Gestational Trophoblastic Neoplasia; Gestational Trophoblastic Disease; Gestational Trophoblastic Neoplasms
• Intervention / Treatment: Drug: MTX 1; Drug: MTX 2; Biological: Act-d

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital，Shandong University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Women's Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients who FIGO Stage I, II, or III criteria for low-risk gestational trophoblastic neoplasia (GTN);
• WHO risk score 0-6;
• Age≤60 years; female, Chinese women;
• Initial treatment is chemotherapy; patients who received prior low-dose methotrexate for treatment of an ectopic pregnancy will be eligible for this study;
• Performance status: Karnofsky score≥60;
• Laboratory tests: WBC≥3.5×10(9)/L, ANC≥1.5×10(9)/L, PLT≥80×10(9)/L, serum bilirubin≤ 1.5 times the upper limit of normal, transaminase≤ 1.5 times the upper limit of normal, BUN, Cr≤ normal
• Provide written informed consent.

Exclusion Criteria:

• Patients with unconfirmed diagnosis of GTN;
• Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)
• WHO risk score >6;
• With severe or uncontrolled internal disease, unable to receive chemotherapy;
• Concurrently participating in other clinical trials
• Unable or unwilling to sign informed consents;
• Unable or unwilling to abide by protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methotrexate Single-coure chemotherapy; Regimen: Methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5. If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen.	Drug: MTX 1; MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5
Experimental: Methotrexate+dactinomycin Single-dose chemotherapy; Regimen: dactinomycin d 0.6mg/m2, IV, on day1, 2; methotrexate 100mg/m2, IV, on day1 (after Act-d); methotrexate 200mg/m2, IVgtt, on day1 (after methotrexate, 500ml NS, >4h). If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen.	Drug: MTX 2; MTX 100mg/m(2), IV, on day1 (after Act-d); MTX 200mg/m(2), IVgtt, on day1 (after MTX, 500ml NS, >4h); Biological: Act-d; Act-d 0.6mg/m(2), IV, on day1,2
Active Comparator: MTX multiple courses chemotherapy; Regimen: methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5, 2-week intervals. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive at least 1 additional consolidation treatment. After treatment, all the patients were asked for contraception with condom or oral contraception. Regular hCG surveillance, once a month for 3 consecutive months and once every 3 months for 2 years, was performed. During follow-up period, pelvic ultrasound and pulmonary X ray or CT scan were conducted if needed.	Drug: MTX 1; MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response (CR) by single-course	through study completion, an average of 1 year
Completely remission rate by multiple courses after single-course failure	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
remission rate of ACTD replacement after MTX resistance	through study completion, an average of 1 year
the number of courses needed to achieve complete remission after multi-course treatment	through study completion, an average of 1 year
complete remission rate by multidrug combination therapy after single drug failure	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Ding Ma
• Collaborators: Shandong University; Huazhong University of Science and Technology; Zhejiang University
• Investigators: Study Chair: Xing Xie, MD, PhD, Zhejiang University

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: March 29, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): December 24, 2019
• Last Update Submitted That Met QC Criteria: December 23, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Pregnancy Complications; Pregnancy Complications, Neoplastic; Neoplasms; Trophoblastic Neoplasms; Gestational Trophoblastic Disease
• Other Study ID Numbers: 2012-GYN/GTN-01