Study of Paclitaxel Plus Cisplatin as the First-line Chemotherapy in High Risk Gestational Trophoblastic Tumor

Study Overview
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Brief Summary
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This clinical trial is designed to study the effect and safety of paclitaxel plus cisplatin as the first-line regimen in the treatment of high risk gestational trophoblastic tumor.

Detailed Description
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Gestational trophoblastic tumor (GTN) is a group of malignant tumors derived from placental trophoblastic cells, most of which occur in women of reproductive age. The survival rate of patients with score of 7 or more points, or WHO Ⅳ period for high-risk patients was of 60% to 80%. However, due to severe toxic reactions, long treatment time, loss of optimal reproductive age and increased costs, and treatment failure caused by chemotherapy resistance, high-risk GTN is still one of the tumors seriously affecting the life health and quality of life of young women. First-line chemotherapy recommended by FIGO is regimen of EMA - CO with corresponding side effects and adverse factors in the following aspects as relatively higer incidence of myelosupression, VP - 16 being associated with a second tumor, especially leukemia, and a definite effect of cyclophosphamide on the failure ovarian function Taxol (Taxol) is the most widely used and most effective broad-spectrum anti-tumor drug in gynecological malignant tumors at present, and T (paclitaxel) +P (platinum drugs) scheme is the first-line chemotherapy scheme in ovarian cancer patients at present. According to references, TP also has effects on resistant and refactory high risk GTN patients. Given relatively simple operation way of TP chemotherapy, and the effect of chemotherapy in recurrence and high-risk refractory GTN performance,this prospective multicenter randomized controlled clinical research was to study the effect and safety of paclitaxel plus cisplatin as the first-line regimen in the treatment of high risk gestational trophoblastic tumor compared with EMA-CO.

Official Title
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A Prospective Randomized Multicenter Clinical Control Study of Paclitaxel Plus Cisplatin as the First-line Chemotherapy in High Risk Gestational Trophoblastic Tumor

Conditions
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Gestational Trophoblastic Neoplasms

Intervention / Treatment
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* Drug: Etoposide
* Drug: actinomycin D
* Drug: methotrexate
* Drug: vincristine
* Drug: cyclophosphamide
* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who International Federation of Gynecology and Obstetrics (FIGO) Stage I, II, or III criteria for high-risk gestational trophoblastic neoplasia (GTN) and stage Ⅳ cases World Health Organization(WHO) risk score ≥7, and less than 13 Age≤60 years; female, Chinese women Initial treatment is chemotherapy 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,blood urea nitrogen, 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 less than 7 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

Ages Eligible for Study
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Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control group<br>etoposide, methotrexate ,actinomycin D,vincristine, cyclophosphamide(EMA-CO), two weeks a cycle | Drug: Etoposide<br>* etoposide 100mg/m2 ivgtt started at the first day of cycle, two weeks a cycle<br>* Other names: VP-16;Drug: actinomycin D<br>* actinomycin D 500ug ivgtt, started at the first day of cycle, two weeks a cycle<br>* Other names: Sanamycin;Drug: methotrexate<br>* methotrexate 100mg/m2, 200mg/m2, ivgtt, tetrahydrofolic acid （FA) 15mg q12h*4(24h after methotrexate injection),started at the first day of cycle, two weeks a cycle<br>* Other names: MTX;Drug: vincristine<br>* vincristine 1mg/m2 started at the 8th day of cycle, two weeks a cycle<br>* Other names: VCR;Drug: cyclophosphamide<br>* cyclophosphamide 600mg/m2, started at the 8th day of cycle, two weeks a cycle<br>* Other names: CTX;|
| Experimental: study group<br>paclitaxel + cisplatin or carboplatin，two weeks a cycle | Drug: Paclitaxel<br>* paclitaxel 135mg/m2, started at the first day of cycle, two weeks a cycle<br>* Other names: Taxol;Drug: Cisplatin<br>* cisplatin 50mg/m2, started at the first day of cycle, two weeks a cycle<br>* Other names: DDP;Drug: Carboplatin<br>* carboplatin area under curve (AUC)=4-5, started at the first day of cycle, two weeks a cycle,as a substitute drug for cisplatin<br>* Other names: CBP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate in firstline treatment | We may calculate the rate of complete response and the rate of treatment failure at the preliminary end point of the trail. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of adverse events as assessed by the WHO | We calculate the adverse events during and after chemotherapy. | 3 years | 
| Overall Survival Rate (OR) | We calculate the overall survival rate of high risk GTN patients after chemotherapy. | 3 years | 
| Ovarian functional evaluation | We may test serum level of anti-mullerian hormone (AMH) every 6 months and the time of menstrual cycle resuming after chemotherapy. | every 6 months up to 3 years | 
| The pregnancy rate | To calculate the pregnancy rate in an actuarial manner using the Kaplan-Meier method at the end of the trail | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gestational trophoblastic tumor, paclitaxel, cisplatin, carboplatin, chemotherapy