The goal of this clinical trial is to assess the feasibility of adding a combination of metformin and turmeric as part of a nutritional intervention regimen to the current standard of care, namely, intermittent Androgen Deprivation Therapy (iADT), for patients with castration sensitive biochemical progressive prostate cancer.
The main objectives are:
* Assess the feasibility of the study population and enrollment. * Evaluate time to PSA relapse with nutritional intervention on iADT.
Participants who are receiving iADT will be dispensed Metformin and turmeric and complete a pill diary. Participants will also have blood and stool samples collected and complete quality of life questionnaires.
The long-term goal is to further assess the efficacy and safety of this nutritional regimen and the roles of metabolic syndrome, microenvironment/microbiome, and genomic vs epigenomic profiles in the care of these patients through a clinical trial.
18 years of age or older.
History of prior prostatectomy and/or radiation therapy to the prostate.
Currently have rising PSA levels ≥ 0.2 ng/ml if they have undergone radical prostatectomy, or a PSA ≥ nadir + 2 if they have received only radiotherapy. Patients who were not offered salvage radiotherapy as an alternative treatment will be considered ineligible (due to a high PSA, other medical concerns).
Currently have at least 2 consecutively rising serum PSA levels more than 1 week apart
Current Chronic Lymphocytic Leukemia (CLL), Monoclonal Gammopathy of Unknown Significance (MGUS), Renal Cell Carcinoma (RCC) or another cancer requiring active treatment. Indolent or stable malignancies such as non-melanoma skin cancers are allowed.
Any active or deteriorating liver or renal disease, Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C or bone marrow deficiency.
Any history of allergic reactions attributed to turmeric, metformin, or other compounds of similar chemical or biologic compositions.
History of lactic acidosis or risk factors for lactic acidosis (e.g., renal impairment, concomitant use of carbonic anhydrase inhibitors such as topiramate, hypoxic states such as acute congestive heart failure, excessive alcohol intake, and hepatic impairment).
Single group
Metformin
DrugSubjects will start with metformin 500 mg by mouth (po) two times daily (bid) with meals for 14 days. Metformin titration will then increase to 850 milligram (mg) po bid for 14 days before increasing titration to a desired dosage of 1,000 mg po bid. For those subjects currently taking Metformin, they will continue current dose (if 1,000 mg po bid) or titrate dose as just described until maximum dose is achieved.
Turmeric
DrugEach subject will start with 1,500 mg turmeric po daily with meals. The dose can be temporarily reduced to 1,000 mg po daily for those who report GI discomfort. If GI discomfort has resolved within one month of the dose reduction, subjects will resume 1,500 mg po daily. If GI discomfort has not resolved or resumes at increased dose, the subject may be instructed to stop taking the study treatment and removed from the study.
Assess feasibility of recruitment
Assessed using frequency (in percentage) of the number of subjects enrolled in the first six and twelve months out of the total desired accrual
Evaluate time to PSA relapse with nutritional intervention on iADT.
Observed from the time of consent to the time of PSA relapse or at the end of the study period (i.e., 27 months), whichever comes first. A survival curve will be used to estimate the accumulated rate of PSA relapse over time (over 27 months).
Quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P), Version 4.
Obtain Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores at baseline, after completion of 8 months of iADT with nutritional intervention, and at the end of the study (i.e., after 27 months). Minimum and maximum values 0-156. Higher scores indicate better outcome.
Quality of Life (QOL) assessed by the Aging Male Symptoms Questionnaire (AMS Questionnaire).
Obtain Aging Male Symptoms Questionnaire (AMS Questionnaire) scores at baseline, after completion of 8 months of iADT with nutritional intervention, and at the end of the study (i.e., after 27 months). Minimum and maximum values 17-85. Higher scores indicate worse outcome.
Expression levels of Metabolomic biomarkers from blood samples
Assessed at baseline, after 8 months of iADT with nutritional intervention, and at 16 months, and will be summarized using mean ± standard deviation and/or median (min, max)
Expression levels of CSC biomarkers including EMT and miRNAS from blood samples
Assessed at baseline, after 8 months of iADT with nutritional intervention, and at 16 months, and will be summarized using mean ± standard deviation and/or median (min, max)
Expression levels of Cancer dormancy Biomarkers (miR-200s, TGF-beta, BMPs, immune and inflammatory factors) from blood samples
Assessed at baseline, after 8 months of iADT with nutritional intervention, and at 16 months, and will be summarized using mean ± standard deviation and/or median (min, max)
Microbiome profiling from the stool samples to assess gut microbiome
Assessed at baseline, after 8 months of iADT with nutritional intervention, and at 16 months, and will be summarized using mean ± standard deviation and/or median (min, max)
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