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

Ding Ma

Status and phase: Unknown; Phase 3

Conditions: Gestational Trophoblastic Tumor; Gestational Trophoblastic Disease; Gestational Trophoblastic Neoplasia; Gestational Trophoblastic Neoplasms

Treatments: Biological: Act-d; Drug: MTX 2; Drug: MTX 1

Study type: Interventional

Funder types: Other

Identifiers

NCT01823315

2012-GYN/GTN-01

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: Female

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

Methotrexate Single-coure chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: MTX 1

Methotrexate+dactinomycin Single-dose chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: MTX 2

Biological: Act-d

MTX multiple courses chemotherapy

Active Comparator group

Description:

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.

Treatment:

Drug: MTX 1