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

Sponsor

Weiguo Lv (Other)

Overall Status

Recruiting

CT.gov ID

NCT02639650

Collaborator

Shandong University (Other), Huazhong University of Science and Technology (Other), First Affiliated Hospital of Zhongshan Medical University (Other)

214

Enrollment

Location

Arms

120

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gestational Trophoblastic Neoplasms	Drug: Etoposide Drug: actinomycin D Drug: methotrexate Drug: vincristine Drug: cyclophosphamide Drug: Paclitaxel Drug: Cisplatin Drug: Carboplatin	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

214 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2016

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: control group etoposide, methotrexate ,actinomycin D,vincristine, cyclophosphamide(EMA-CO), two weeks a cycle	Drug: Etoposide etoposide 100mg/m2 ivgtt started at the first day of cycle, two weeks a cycle Other Names: VP-16 Drug: actinomycin D actinomycin D 500ug ivgtt, started at the first day of cycle, two weeks a cycle Other Names: ACTD Sanamycin Drug: methotrexate methotrexate 100mg/m2, 200mg/m2, ivgtt, tetrahydrofolic acid （FA) 15mg q12h4(24h after methotrexate injection),started at the first day of cycle, two weeks a cycle Other Names: MTX Drug: vincristine* vincristine 1mg/m2 started at the 8th day of cycle, two weeks a cycle Other Names: VCR Drug: cyclophosphamide cyclophosphamide 600mg/m2, started at the 8th day of cycle, two weeks a cycle Other Names: CTX
Experimental: study group paclitaxel + cisplatin or carboplatin，two weeks a cycle	Drug: Paclitaxel paclitaxel 135mg/m2, started at the first day of cycle, two weeks a cycle Other Names: Taxol Drug: Cisplatin cisplatin 50mg/m2, started at the first day of cycle, two weeks a cycle Other Names: DDP Drug: Carboplatin carboplatin area under curve (AUC)=4-5, started at the first day of cycle, two weeks a cycle,as a substitute drug for cisplatin Other Names: CBP

Arm

Intervention/Treatment

Active Comparator: control group

etoposide, methotrexate ,actinomycin D,vincristine, cyclophosphamide(EMA-CO), two weeks a cycle

Drug: Etoposide

etoposide 100mg/m2 ivgtt started at the first day of cycle, two weeks a cycle

Other Names:

VP-16

Drug: actinomycin D

actinomycin D 500ug ivgtt, started at the first day of cycle, two weeks a cycle

Other Names:

ACTD

Sanamycin

Drug: methotrexate

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

Other Names:

MTX

Drug: vincristine

vincristine 1mg/m2 started at the 8th day of cycle, two weeks a cycle

Other Names:

VCR

Drug: cyclophosphamide

cyclophosphamide 600mg/m2, started at the 8th day of cycle, two weeks a cycle

Other Names:

CTX

Experimental: study group

paclitaxel + cisplatin or carboplatin，two weeks a cycle

Drug: Paclitaxel

paclitaxel 135mg/m2, started at the first day of cycle, two weeks a cycle

Other Names:

Taxol

Drug: Cisplatin

cisplatin 50mg/m2, started at the first day of cycle, two weeks a cycle

Other Names:

DDP

Drug: Carboplatin

carboplatin area under curve (AUC)=4-5, started at the first day of cycle, two weeks a cycle,as a substitute drug for cisplatin

Other Names:

CBP

Outcome Measures

Primary Outcome Measures

complete remission rate in firstline treatment [3 years]
We may calculate the rate of complete response and the rate of treatment failure at the preliminary end point of the trail.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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