Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000310167
Ethics application status
Approved
Date submitted
5/02/2019
Date registered
28/02/2019
Date last updated
20/09/2022
Date data sharing statement initially provided
28/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Vitamin C for endometrial cancer
Scientific title
Vitamin C for Endometrial Cancer: A pilot study to assess the cellular impact of pre-operative high dose vitamin C administration in women with endometrial cancer
Secondary ID [1] 297051 0
Nil known.
Universal Trial Number (UTN)
U1111-1226-6498
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer 311046 0
Condition category
Condition code
Cancer 309686 309686 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study comprises a surgical window-style study design with an intervention administered between diagnosis and planned surgical resection.
1. Following diagnosis of endometrial cancer and informed consent, prior to planned elective surgery, tumour tissue will be collected by pipelle biopsy. This biopsy is in addition to standard care, and it will be taken in an outpatient setting. The pipelle biopsy is a commonly performed outpatient procedure and in fact many patients will have experienced this as their diagnostic procedure. The procedure involves insertion of a vaginal speculum and the introduction of a fine plastic tube into the uterus. Material from within the uterine cavity is sucked into the tube by applying negative pressure. For the purpose of the study the biopsy will be performed by the named clinical investigators who are highly experienced at this procedure, and the patients will have a good understanding of the required procedure. Appropriate oral and local analgesia will be given in consultation with the patient. The procedure will be performed in a safe clinical environment with appropriate analgesia and a nurse assistant. Adverse events associated with the pipelle biopsy will be recorded.
2. Patients usually proceed to surgery approximately two – four weeks from the initial diagnostic biopsy. Within this time frame, Vitamin C administration will be co-ordinated to start five days before the planned surgical removal of the endometrial tumour.
2. Vitamin C will be administered by intravenous infusion daily for four days prior to surgery, beginning with a dose of 25 g, then 1g/kg capped at a maximum of 75 g.
3. Blood samples will be collected at the time of pipelle biopsy, and then daily for four days prior to and after high dose vitamin C (HDVC).
Intervention code [1] 313327 0
Treatment: Other
Comparator / control treatment
Control patients will undergo the initial pipelle biopsy, but will not receive vitamin C infusions. Blood samples will be collected at the time of the pipelle biopsy and at surgery. Tumour tissue not required for diagnostic purposes will also be retrieved following planned surgery (hysterectomy).
Control group
Active

Outcomes
Primary outcome [1] 318653 0
1. Measurement of ascorbate levels in endometrial tumour tissue in biopsy samples and post-ascorbate treatment surgical specimens.
Timepoint [1] 318653 0
Biopsy samples taken at recruitment. Vitamin C infusions given for 4 consecutive days immediately prior to surgery (day 5). Tumour tissue obtained post-surgery.
Primary outcome [2] 318654 0
2. Determination of the composite outcome of the association between ascorbate and the upregulation of the tumour hypoxic pathway, as assessed by the measurement of the HIF-1, VEGF, BNIP3, and CA-IX proteins and tumour ascorbate.
Timepoint [2] 318654 0
Biopsy samples taken at recruitment. Vitamin C infusions given for 4 consecutive days immediately prior to surgery (day 5). Tumour tissue obtained post-surgery.
Secondary outcome [1] 365592 0
Effects on immune cell infiltration and micro-vessel density as assessed by histological examination with immuno-staining.
Timepoint [1] 365592 0
Tumour tissue obtained at time of recruitment and at surgery (up to one month apart, depending on surgery schedule).
Secondary outcome [2] 365593 0
Vitamin C levels in blood samples before, during and after HDVC administration are recorded.
Timepoint [2] 365593 0
Blood samples taken at time of pipelle biopsy, daily for 4 consecutive days together with vitamin C infusions, and on day of surgery (day 5).
Secondary outcome [3] 365594 0
Estimation of patient acceptance of proposed schedule i.e. additional pipelle biopsy taken prior to surgery, receiving four (daily) IV infusions, providing four (daily) blood samples. This will be determined by recording the number of recruited patients as a percentage of those approached to take part in the study.
Timepoint [3] 365594 0
At time of recruitment.
Secondary outcome [4] 365595 0
Determination of the adequacy of the amount and quality of tissue sample obtained for analysis from biopsy or surgical material at the planned time points. Minimum amount of tissue to be 100 mg, of which 90% is histologically verified as tumour tissue.
Timepoint [4] 365595 0
Tumour tissue obtained at time of recruitment and at surgery (up to one month apart, depending on surgery schedule).
Secondary outcome [5] 367524 0
Changes in epigenetic methylation marks on histones and DNA monitored by mass spectroscopy and immuno-detection.
Timepoint [5] 367524 0
Tumour tissue obtained at time of recruitment and at surgery (up to one month apart, depending on surgery schedule)

Eligibility
Key inclusion criteria
1. Confirmed endometrial cancer clinically confined to the uterus via biopsy histology with a plan to undergo hysterectomy.
2. Good physical functional status – ECOG grade 0 or 1.
3. Aged greater than or equal to 18 years.
4. Adequate bone marrow, hepatic, renal and cardiac function as determined by treating clinician
5. Willing to undergo an additional pipelle biopsy prior to surgery and able to come to the Christchurch Clinical Studies Trust research unit daily for four days prior to surgery for IV vitamin C infusions.
6. Able to give informed consent to participate in the study.
Minimum age
18 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receiving neoadjuvant therapy.
2. Pipelle biopsy prior to hysterectomy is not feasible or was unsuccessful.
3. Adverse response to test dose of 25 g IV vitamin C given on the first intervention day.
4. Supplementing with vitamin C greater than or equal to 1 g/d, within the last 3 months.
5. Serum creatinine concentration greater than 150 µmol/L.
6. Erythrocyte glucose-6-phosphate dehydrogenase activity deficiency (participants will be tested for this).
7. Uncontrolled hypertension (levels greater than 150/95), or plasma sodium higher than the upper limit of normal.
8. Serious gastrointestinal disorders including active bleeding.
9. Patients with serious or uncontrolled infection, cardiac or neurological conditions.
10. Inability to give informed consent for any reason, including cognitive problems or altered mental status.
11. Pregnant or lactating women.
12. Any abnormal laboratory value or medical condition that would, in the investigators’ judgement, make the patient a poor candidate for the study.
13. Current calcium oxalate nephropathies with the potential to block urinary flow.
14. Individuals who require blood sugar monitoring for diabetes (as HDVC can have a hypoglycaemic effect and can also interfere with some glucose finger stick devices).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be achieved with use of sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random numbers generation and allocation by sealed opaque envelopes
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
For analysis of the tumour samples and to determine the difference before and after treatment with IV vitamin C or between vitamin C and control samples, data will be analysed using GraphPad Prism or SPSS® 13.0 for Windows.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
22/08/2019
Date of last participant enrolment
Anticipated
30/06/2024
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
21
Accrual to date
10
Final
Recruitment outside Australia
Country [1] 21194 0
New Zealand
State/province [1] 21194 0
CANTERBURY

Funding & Sponsors
Funding source category [1] 301621 0
University
Name [1] 301621 0
University of Otago
Country [1] 301621 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago, Christchurch,
PO Box 4345,
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 301324 0
None
Name [1] 301324 0
Address [1] 301324 0
Country [1] 301324 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302347 0
Health and Disability Ethics Committees
Ethics committee address [1] 302347 0
Ethics committee country [1] 302347 0
New Zealand
Date submitted for ethics approval [1] 302347 0
30/01/2019
Approval date [1] 302347 0
19/02/2019
Ethics approval number [1] 302347 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89906 0
A/Prof Peter Sykes
Address 89906 0
Department of Obstetrics and Gynaecology and Christchurch Women’s Hospital.,
University of Otago, Christchurch,
PO Box 4345,
Christchurch 8140
Country 89906 0
New Zealand
Phone 89906 0
+64 3 364 4630
Fax 89906 0
Email 89906 0
[email protected]
Contact person for public queries
Name 89907 0
Margreet Vissers
Address 89907 0
Department of Pathology and Biomedical Science.
University of Otago, Christchurch,
PO Box 4345,
Christchurch 8140
Country 89907 0
New Zealand
Phone 89907 0
+64 3 364 1524
Fax 89907 0
Email 89907 0
[email protected]
Contact person for scientific queries
Name 89908 0
Margreet Vissers
Address 89908 0
Department of Pathology and Biomedical Science.
University of Otago, Christchurch,
PO Box 4345,
Christchurch 8140
Country 89908 0
New Zealand
Phone 89908 0
+64 3 364 1524
Fax 89908 0
Email 89908 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After de-identification, individual participant data underlying published results only will be shared.
When will data be available (start and end dates)?
Immediately following results publication and ending 5 years following publication.
Available to whom?
Case-by-case basis at the discretion of the primary sponsor
Available for what types of analyses?
Only to achieve the aims in the approved proposal.
How or where can data be obtained?
Access subject to approvals by Principal Investigator, requirement to sign data access agreement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7164Study protocol  [email protected]
7165Informed consent form  [email protected]
7166Ethical approval  [email protected]



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.