None listed
Conditions
Brief summary
Vitamin C has many roles in mammalian biology, and a number are identified as being potentially relevant for cancer growth and therapy. The transcription factor hypoxia-inducible factor (HIF) -1 that regulates the cell response to oxygen deprivation is a known driver of cancer growth and resistance to therapy and the inactivation of HIF-1 is dependent on intracellular vitamin C. This connection between intracellular vitamin C and HIF-1 activation has led to the hypothesis that increasing vitamin C levels in tumours will down-regulate HIF-1 and associated markers of tumour growth and aggression. In this pilot study we aim to investigate whether administration of vitamin C by high dose intravenous infusion results in increased tumour vitamin C levels in women with endometrial cancer. We also aim to assess the cellular impact of pre-operative high dose intravenous vitamin C administration in these cancers. This study comprises a surgical window-style study design with an intervention administered between diagnosis and planned surgical resection. Following diagnosis of endometrial cancer and informed consent, prior to planned elective surgery, tumour tissue will be collected by an additional procedure to obtain a pipelle biopsy. Tumour tissue not required for diagnostic purposes will also be retrieved following planned surgery (hysterectomy). The consented cohort will be divided into control patients and those receiving HDVC (ratio of 1:2 control to treated), which will be administered daily for four days prior to surgery, beginning with a dose of 25 g, then 1g/kg capped at a maximum of 75 g. Blood samples will be collected at the time of pipelle biopsy, and then daily for four days prior to and after HDVC. Control patients will not receive infusions. Our study will include evaluation of vitamin C levels and cell HIF-1 activity modulation before and after vitamin C exposure, in the biopsy specimen and the surgical specimen respectively. The purpose of the study is to determine the potential mechanism of anti-tumour activity to guide future clinical study designs and to identify the potential for the therapeutic effect of vitamin C in this disease.
Interventions
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 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).
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
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.
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).
Outcome results
None listed