None listed
Conditions
Brief summary
The primary purpose of this trial is to evaluate the safety and tolerability of Metformin (MET) in combination with sodium valproate (VPA) for the treatment of prostate cancer. Who is it for? You may be eligible to participate in this trial if you are aged 18 or over and have been diagnosed with localised or locally advanced prostate cancer for which radical prostatectomy is planned within the next 6-8 weeks. Study details Participants enrolled in this trial will receive a combination of MET and VPA in increasing doses depending on the cohort they are enrolled in. The study drugs will be administered for a total of 4 weeks just prior to the planned surgery for removing the prostate It is hoped that this trial will provide information on the optimal dose of MET plus VPA to administer to prostate cancer patients, which may be an effective treatment which is safe and tolerated by patients.
Interventions
Combination of sodium valproate and metformin will be administered as oral tablets.
Three dose levels of the drugs are planned. First level – a fixed dose of Met and VPA at 500 mg twice daily will be given to the participants. If no dose limiting toxicity is seen in this cohort I (N=3), after the 4 weeks of drug administration, participants will be next dosed at level 2 dosing where the starting dose is 500 mg twice daily for both drugs. In this cohort II (N=3), Met dose alone will be increased
Combination of sodium valproate and metformin will be administered as oral tablets. Three dose levels of the drugs are planned. First level – a fixed dose of Met and VPA at 500 mg twice daily will be given to the participants. If no dose limiting toxicity is seen in this cohort I (N=3), after the 4 weeks of drug administration, participants will be next dosed at level 2 dosing where the starting dose is 500 mg twice daily for both drugs. In this cohort II (N=3), Met dose alone will be increased to 1000 mg twice daily from week 2 onwards while VPA dose will be maintained at 500 mg twice daily. If no dose limiting toxicity is seen in this cohort II, subjects will be dosed at next dose level. Subjects in this cohort III (N=6) will have both the drug doses increased from the starting dose of 500 mg twice daily to 1000 mg twice daily sequentially. Dose escalation will not proceed beyond the 1000 mg twice daily schedule. Participants in cohort I will receive 4 weeks on Met and VPA 500mg each twice daily; cohort II week 1 Met and VPA 500mg each twice daily then Met 1000mg and VPA 500mg twice daily from week 2 -4; cohort III week 1 Met and VPA 500mg each twice daily then Met 1000mg and VPA 500mg twice daily from week 2; then Met 1000 mg and VPA 1000 mg twice daily week 3-4. All study drugs will be ceased at least 48 hours but no more than 7 days prior to surgery. Participants will be requested to return any left over tablets.
Sponsors
Flinders University
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1 Patients must have histologically confirmed localized or locally advanced prostate cancer – Clinical stage T1c or T2 with high-grade disease (Gleason's 8-10) on initial biopsy, or clinical stage T2b-T2c with Gleason's grade >/= 7 and PSA > 10ng/ml. 2 Must be planned for radical prostatectomy within the next 6-8 weeks 3 No documented metastatic disease on CT or Bone scans. Prostate specific Membrane antigen (PSMA) PET scans allowed – but, not mandatory for establishing non-mestastatic disease 4 Age >18 years. 5 ECOG performance status <1 6 Life expectancy of greater than 12 months 7 Patients must have normal organ and marrow function 8 Not planned for Androgen deprivation therapy 9 Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1 Patients who have had chemotherapy or radiotherapy or metformin or sodium valproate 2 Patients may not be receiving any other investigational agents. 3 Patients with known metastases 4 History of allergic reactions attributed to compounds of similar chemical composition to the agents used in study. 5 Patients receiving any medications or substances that are inhibitors or inducers of CYP450 3A4 are ineligible. Lists including medications and substances known or with the potential to interact with CYP450 3A4 isoenzymes are provided in product information of the study drugs. 6 Past history of pancreatitis, extensive bowel resection, known urea cycle disorders or porphyria 7 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 8 Patients with diabetes or known epilepsy
Outcome results
None listed