A Multicenter, Prospective, Randomized Trial of Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 300
- 试验地点
- 3
- 主要终点
- Complete response (CR) by single-course
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: MTX 1 (Drug)
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.
干预措施: MTX 2 (Drug)
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.
干预措施: Act-d (Biological)
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.
干预措施: MTX 1 (Drug)
结局指标
主要结局
Complete response (CR) by single-course
时间窗: through study completion, an average of 1 year
Completely remission rate by multiple courses after single-course failure
时间窗: through study completion, an average of 1 year
次要结局
- the number of courses needed to achieve complete remission after multi-course treatment(through study completion, an average of 1 year)
- remission rate of ACTD replacement after MTX resistance(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)
研究者
Ding Ma
Director of the department of Obstetrics and Gynecology, Tongji Hospital
Huazhong University of Science and Technology