Plain English Summary
Background and study aims
Gestational trophoblastic neoplasm (GTN) is a type of neoplastic (tumor-like) condition after normal or abnormal pregnancy. This condition is usually resolved with initial diagnostic as well as therapeutic minor surgical procedure. After diagnosis of this condition, a few of them demonstrate persistent abnormality. This condition is treated with chemotherapy and is curable most of the time. There are different regimens to treat with chemotherapy and the most common ones require 5-8 days to complete a single cycle of treatment. This trial uses a less frequent dosing regimen that is completed in 2-3 days. The control treatment involves conventional regimen of alternate day injections for a week every 2 weeks and another experimental regimen involves two drugs each given only once every 2 weeks in a higher dose. Both of these drugs are approved but in different doses and dosing intervals. A less frequent dosing interval can increase patient compliance due to reduced duration of hospital admissions, less cost and operational feasibility in the hospital if the hypothesis is proven. This trial involves research and the purpose is to treat the GTN with two different regimens.
Participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled. Treatment regimen will be assigned randomly to assure equal chance of getting either treatment regimen.
Only low risk choriocarcinoma or persistent mole will be taken for the trial and participant should use effective contraception during the trial period. Trial period will extend up to 4 months. There will be blood work in the beginning and every two weeks thereafter. Chest X-ray and abdominal sonography will be done in the beginning.
Who can participate?
Women aged 18 years or over with post-molar GTN or choriocarcinoma, who have no other cancers and who are not breast-feeding.
What does the study involve?
Patients will be randomized to receive one of two combinations of chemotherapy drugs.
What are the possible benefits and risks of participating?
Participants in study arm might benefit from a shorter hospital stay compared with those in the control arm. All trial drugs have the potential for side effects. Compensation and/or treatment is available to the subject in the event of trial-related injury. There is no extra incentive of any kind besides treatment required by the research. Treatment protocol will be as an intention to treat and lab tests and chemotherapeutic agents will be used as per usual practice. Thus there is no added cost to the patient.
Where is the study run from?
Paropakar Maternity and Women's Hospital, Kathmandu and other collaborating hospitals in Nepal
When is the study starting and how long is it expected to run for?
The study started in January 2018 and is expected to run for approximately 2 years.
How long will the trial be recruiting participants for?
The trial will be recruiting for approximately 11 months.
Who is the main contact?
Dr Gehanath Baral (gehanath@gmail.com)
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1
Study information
Scientific title
A phase III randomized trial of multi-day methotrexate versus biweekly pulse of methotrexate and actinomycin for the treatment of low-risk gestational trophoblastic neoplasia.
Acronym
Study hypothesis
Less frequent combination treatment is not inferior to the multi-day single drug treatment in patients with low-risk gestational trophoblastic disease with respect to complete response.
Ethics approval
Institutional Review Board, National Academy of Medical Sciences (IRB-NAMS), 27/06/2017, RG18-2017
Study design
phase III non-inferiority randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Gestational trophoblastic neoplasia (GTN)
Intervention
Block randomization was done online at the site: https://www.sealedenvelope.com/simple-randomiser/v1/lists.
Experimental arm: Patients receive methotrexate 200 mg/m2 IV in 500 ml NS over 12 hours plus actinomycin 1 mg IV followed 24 hours later by folinic acid 15 mg PO/IV/IM BD for 2 days; cycle repeats every 2 weeks.
Active comparator arm: Patients receive methotrexate 50mg/m2 IM on days 1, 3, 5, and 7 and folinic acid 5 mg IV on days 2, 4, 6, and 8; cycle repeats every 2 weeks.
Follow-up will be at each 2-weekly cycle of chemotherapy, with 3-4 months required to complete the treatment cycle. Patients will be followed up for at least 1 year as per clinical protocol followed by the hospital.
Intervention type
Drug
Phase
Phase III
Drug names
Active comparator arm: Methotrexate and folinic acid
Experimental arm: Methotrexate, folinic acid and actinomycin
Primary outcome measure
Time to achieve serum β-hCG <5 mU/ml measured using the blood test at clinical laboratory of study site as a routine practice in the hospital prior to recruitment and then every 2 weeks before commencing each subsequent chemotherapy cycle until the level comes down to normal for two timepoints.
Secondary outcome measures
1. Total hospital admission days is measured using source document from treatment and discharge date.
2. Compliance to complete therapy is measured using defined follow up dates and rate of defaulter.
3. Need of high-risk regimen is measured by switch over into high-risk treatment regimen (if any).
4. Need of surgical intervention is measured using type of treatment received in each visit cycle.
Overall trial start date
01/01/2018
Overall trial end date
31/12/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically proven post molar GTN (Persistent mole for ≥4 months) or choriocarcinoma
2. Female
3. Age 18 years or above
4. WHO risk score of 6 or less
5. Willing to practice effective contraception for the duration of the study
6. Consented for participation
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Maximum of 120
Participant exclusion criteria
1. Lactating
2. PSTT, non-gestational neoplasia
3. Abnormal CBC, LFT,RFT
4. Cancers in other organs
Recruitment start date
29/01/2018
Recruitment end date
31/12/2018
Locations
Countries of recruitment
Nepal
Trial participating centre
Paropakar Maternity and Women's Hospital
Thapathali
Kathmandu
GPO 8975 EPC 1553, Kathmandu, Nepal
Nepal
Funders
Funder type
Other
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
It will be disseminated at the trial site and published in a peer reviewed journal. Presentation in professional society meetings/conferences.
IPD sharing statement: The data sharing plans for the study are unknown and will be made available at a later date
Intention to publish date
31/12/2019
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list