Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001118392
Ethics application status
Approved
Date submitted
11/07/2017
Date registered
31/07/2017
Date last updated
8/05/2019
Date data sharing statement initially provided
8/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment of ectopic pregnancies of participants with vinorelbine tablets.
Scientific title
Safety and efficacy of oral vinorelbine in treatment of ectopic pregnancies
Secondary ID [1] 292391 0
Nil known
Universal Trial Number (UTN)
Trial acronym
VINO trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ECTOPIC PREGNANCY 304009 0
Condition category
Condition code
Reproductive Health and Childbirth 303340 303340 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Given the promising in vitro and in vivo data, coupled with vinorelbine’s established safety and tolerability profiles in the treatment of human oncology patients, we now wish to progress this concept to the clinic. We hope to recruit 20 participants with stable ectopic pregnancies and treat them each with 2 doses of 60mg/m² of oral vinoralbine, spaced one week apart, instead of methotrexate. The primary aims of this study are to assess the safety, toxicity and tolerability profiles of vinorelbine when administered exclusively to a cohort of women with stable ectopic pregnancies.
Intervention code [1] 298589 0
Treatment: Drugs
Comparator / control treatment
No control group in this study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302728 0
The primary objective of this study is to assess the safety, toxicity and tolerability of administering vinorelbine to patients with ectopic pregnancies with blood tests.
Timepoint [1] 302728 0
The end (resolution) of the ectopic pregnancy – either when serum hCG levels return to less than 5; or when the pregnancy is surgically excised. Participants will have FBC, U&Es, LFTs and hCG done on day 0, day 4 and day 7 to test for neutropaenia and any derangement in liver enzymes.
Secondary outcome [1] 336837 0
Length of time from treatment initiation to resolution of ectopic pregnancy by review of medical records.
Timepoint [1] 336837 0
The end (resolution) of the ectopic pregnancy – either when serum hCG levels return to less than 5; or when the pregnancy is surgically excised,t
Secondary outcome [2] 337420 0
Failure of medical management . Clinical signs and symptoms of a ruptured ectopic.
Timepoint [2] 337420 0
Within 30 days post documented resolution of ectopic pregnancy

Eligibility
Key inclusion criteria
• Aged 18-50 years old
• English speaking
• Able to provide informed consent to participate
• A diagnosis of a tubal ectopic pregnancy on transvaginal ultrasound
• A stable ectopic pregnancy (no evidence of bleeding or rupture)
• A pre-treatment serum Human Chorionic Gonadotrophin (hCG) level of 1,000 – 3,000 IU/L
• Adnexal mass less than or equal to 3.0 cm, with no fetal cardiac activity
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Unable to provide informed consent to participate
• A multiple pregnancy
• Contraindication(s) to vinorelbine or to medical management of ectopic pregnancy
• Immunodeficiency disorder(s)
• A current malignancy
• Received chemotherapy or radiation therapy in the previous five years
• Concomitant disease which could significantly impair gastric absorption (Inflammatory bowel disease, coeliac, etc.)
• History of surgical resection of the stomach/small bowel
• Breastfeeding
• Hepatic impairment, renal impairment, or haematological toxicity

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical analysis for this study will be performed using GraphPad Prism 6 (GraphPad Software, La Jolla, CA). Given the study design and objectives of this particular trial:
• There is no comparison arm, so clinical variables and the clinical course will be presented as descriptive statistics
• There is no power calculation to perform
• Continuous variables will be statistically analysed using a t-test (parametric) or a Mann-Whitney test (non-parametric), as appropriate
• Categorical variables will be statistically analysed using a chi-squared test or Fisher’s exact test, as appropriate
• Biochemical pathology results will be assessed as continuous variables
• A p value of <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2018
Actual
9/08/2018
Date of last participant enrolment
Anticipated
4/02/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
10
Final
Recruitment outside Australia
Country [1] 9047 0
New Zealand
State/province [1] 9047 0
Auckland

Funding & Sponsors
Funding source category [1] 296946 0
Hospital
Name [1] 296946 0
Prathima Chowdary
Country [1] 296946 0
New Zealand
Primary sponsor type
Hospital
Name
North Shore Hospital
Address
North Shore Hospital,
124 Shakespeare Road,
Takapuna,
Auckland 0620, NZ
Country
New Zealand
Secondary sponsor category [1] 295950 0
None
Name [1] 295950 0
Address [1] 295950 0
Country [1] 295950 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298151 0
Health and Disability Ethics Committee
Ethics committee address [1] 298151 0

Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 298151 0
New Zealand
Date submitted for ethics approval [1] 298151 0
03/08/2017
Approval date [1] 298151 0
02/02/2018
Ethics approval number [1] 298151 0

Summary
Brief summary
Ectopic pregnancies are pregnancies that occur outside of the womb, with the vast majority located in the Fallopian tube (the tube which carries a fertilised egg to the womb). They are potentially life threatening as they can erode maternal blood vessels and cause fatal internal bleeding. They are relatively common, representing around 2% of pregnancies.

If an ectopic pregnancy is identified early and is small in size, a drug called methotrexate can be administered via injection. However, only a small number of ectopic pregnancies (~25%) are identified early enough to be suitable for this medication. Additionally, methotrexate is unsuccessful in treating ectopic pregnancies in up to 30% of cases. This means that the majority of ectopic pregnancies are ultimately removed surgically. This exposes many affected women to both surgical and anaesthetic risks; is complex (requiring doctors with specialist surgical skills); and can involve the removal of the woman’s Fallopian tube. As fertility preservation is an important concern in this area of medicine, the development of a new medical therapy with a higher success rate than methotrexate would be a major advance in the clinical care of women who have ectopic pregnancies.

Excitingly, we have discovered in pre-clinical laboratory studies that vinorelbine, an orally available chemotherapeutic medication, may be appropriate for use as an alternative to methotrexate in the medical treatment of ectopic pregnancies. Specifically, we have found in our laboratory studies that vinorelbine is 1,000 to 10,000 times more effective than methotrexate at killing placental cells, is more effective than methotrexate in an animal model ectopic pregnancy, does not cause cell death of donated human Fallopian tubes and does not impact upon subsequent breeding in mice (after a four week washout period). Together, these findings indicate that vinorelbine may not impede future fertility, and that may be an efficacious treatment for ectopic pregnancy.

Given these promising pre-clinical results, we hope to progress this concept and eventually translate these laboratory findings into clinical care. We propose to begin this process with a proof-of-concept, early phase clinical trial. We will recruit 20 women with stable ectopic pregnancies and treat the participants with two doses of 60mg/m² of oral vinorelbine, spaced one week apart. We will assess the safety, toxicity and tolerability of vinorelbine therapy in these women, as well as monitoring the effectiveness of vinorelbine in killing placental cells and resolving ectopic pregnancies. If successful, we will gain sufficient evidence to progress our investigations of vinorelbine as a treatment for ectopic pregnancies to a large-scale, randomized clinical trial. We hope that it may form the basis for an efficient and safe future medical treatment option for this group of women who do not wish to undergo surgery or have their tube removed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76150 0
Dr Prathima Chowdary
Address 76150 0
Waitemata District Health Board
North Shore Hospital
Auckland 0620, NZ
Country 76150 0
New Zealand
Phone 76150 0
+6494868900
Fax 76150 0
Email 76150 0
prath1mak@yahoo.co.in
Contact person for public queries
Name 76151 0
Dr Prathima Chowdary
Address 76151 0
Waitemata District Health Board
North Shore Hospital
Auckland 0620, NZ
Country 76151 0
New Zealand
Phone 76151 0
+6494868900
Fax 76151 0
Email 76151 0
prath1mak@yahoo.co.in
Contact person for scientific queries
Name 76152 0
Dr Prathima Chowdary
Address 76152 0
Waitemata District Health Board
North Shore Hospital
Auckland 0620, NZ
Country 76152 0
New Zealand
Phone 76152 0
+6494868900
Fax 76152 0
Email 76152 0
prath1mak@yahoo.co.in

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1983Informed consent form    373273-(Uploaded-02-05-2019-18-54-36)-Study-related document.doc
1984Ethical approval    373273-(Uploaded-02-05-2019-18-55-54)-Study-related document.pdf


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1983Informed consent formsupporting document attached prath1mak 373273-(Uploaded-02-05-2019-18-54-36)-Study-related document.doc
1984Ethical approval    373273-(Uploaded-15-09-2021-07-04-02)-Study-related document.docx

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.