Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

NCT01823315 | Unknown Phase 3 DMC

• 1 other identifier: 2012-GYN/GTN-01
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Gestational Trophoblastic Disease; Gestational Trophoblastic Neoplasia; Gestational Trophoblastic Tumor; Gestational Trophoblastic Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (3)

Methotrexate Single-coure chemotherapy

EXPERIMENTAL

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

Methotrexate+dactinomycin Single-dose chemotherapy

EXPERIMENTAL

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; Biological: Act-d

MTX multiple courses chemotherapy

ACTIVE COMPARATOR

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

Interventions

MTX 1 DRUG

MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5

MTX multiple courses chemotherapy; Methotrexate Single-coure chemotherapy

MTX 2 DRUG

MTX 100mg/m(2), IV, on day1 (after Act-d); MTX 200mg/m(2), IVgtt, on day1 (after MTX, 500ml NS, \>4h)

Methotrexate+dactinomycin Single-dose chemotherapy

Act-d BIOLOGICAL

Act-d 0.6mg/m(2), IV, on day1,2

Methotrexate+dactinomycin Single-dose chemotherapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ding Ma: lead
• Zhejiang University: collaborator
• Huazhong University of Science and Technology: collaborator
• Shandong University: collaborator

Study Sites (3)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Qilu Hospital，Shandong University

Jinan, Shandong, 250012, China

Location

Women's Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310006, China

Location

MeSH Terms

Conditions

Gestational Trophoblastic Disease

Interventions

Dactinomycin

Condition Hierarchy (Ancestors)

Trophoblastic Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Pregnancy Complications, Neoplastic; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Xing Xie, MD, PhD

  Zhejiang University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the department of Obstetrics and Gynecology, Tongji Hospital

Study Record Dates

• First Submitted: March 21, 2013
• First Posted: April 4, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2019
• Last Updated: December 24, 2019

Record last verified: 2019-12

Locations

CN (3)