Study of Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients Receiving Androgen Deprivation Therapy

Study Overview
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Brief Summary
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The purpose of this study is to look at the effect that the study drug OPC has on AGE levels in patients with prostate cancer.

Detailed Description
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AGEs are a type of metabolite, or substance, found in the food. The AGE content in food is determined by the types of food you eat and also how you prepare your food. The researchers helping conduct this study have found a potential link between AGE levels and cancer. The purpose of this study is to see if Oligomeric Procyanidin Complex (OPC) has an effect on the AGE levels in your blood and to see if those AGE levels have an effect on your cancer.

Official Title
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Randomized Phase II Study of Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients Receiving Androgen Deprivation Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Metformin
* Other: OPC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Confirmation of adenocarcinoma of the prostate that is documented by one of the following: pathology report or clinic note with documented history of prostate cancer. Subjects must be receiving ADT with a GnRH agonist or antagonist, with or without an anti-androgen, with a current testosterone level documented to be <50ng/dL at enrollment. Subjects whose ADT is interrupted may enroll or continue on study as long as the testosterone is documented to remain <50ng/dL for the entire duration of study participation. Subjects who have undergone orchiectomy are also eligible. Prior cytotoxic chemotherapy for metastatic prostate cancer; prior treatment with genomically-targeted agents, or Provenge is allowed. Subjects must have adequate hematologic, renal, and hepatic function at baseline, as follows: Hematology parameters: ANC >1000/mcL, platelets > 100,000/mcL, Hgb >8.0gm/dL Renal Function: eGFR of > 45mls/min using Cockgroft and Gault formula (see appendix C). Liver Function: Total bilirubin ≤ULN, AST and ALT <1.5xULN Able to swallow and retain oral medication ECOG performance status of 0 - 2 Ability to sign written informed consent Testosterone level <50ng/dL Exclusion Criteria Known allergy to grapes or grape seed History of receiving more than 2 classes of ADT. Current use of strong antioxidants (extracts from grape seed, milk thistle; pine bark, green tea, saw palmetto; resveratrol; flavonoids; catechins; ellagic acid), large quantities of red grapes, white button mushrooms, red wine. See section 4.7 for more details.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPC<br>Subjects will take one OPC capsule at the same time each morning and evening, approximately 12 hours apart during weeks 1-12. | Drug: Metformin<br> <br> Other: OPC<br>* OPC is a derivative of grape seed extract<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AGE level reduction | The primary objective is to determine if any of the test agent are able to reduce AGE levels by an average of 30% (or greater) in 50% or more of test subjects. | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between changes to AGE level and changes to PSA |  | 85 days | 
| Correlation between changes to AGE level and changes to BMI |  | 85 days | 
| Correlation between changes to AGE level and changes to insulin resistance (HOMA-IR) |  | 85 days | 
| Correlation between changes to AGE level and changes to A1C. |  | 85 days | 
| Correlations between changes to AGE level and changes to testosterone. |  | 85 days | 
| Correlation between changes to AGE level and changes to lipids. |  | 85 days | 
| Correlation between changes to AGE level and changes to diet. |  | 85 days | 
| Correlation between changes to AGE level and changes to quality of life |  | 85 days | 
| Frequency of adverse events as assessed by CTCAE v. 4 | Toxicities will be tabulated per arm by type and grade and the proportion of patients with grade 3, grade 4 or an SAE will be estimated with a 90% confidence interval. | 85 days | 
| Correlation between AGE levels and plasma IL6 |  | 85 days | 
| Correlation between AGE levels and leptin |  | 85 days | 
| Correlation between AGE levels and c-reactive protein (CRP) |  | 85 days | 
| Correlation between AGE levels and malondialdehyde (MDA) |  | 85 days | 
| Correlation between AGE levels and oxLDLs (low density lipoprotein) |  | 85 days | 
| Correlation between AGE levels and sRAGE (soluble receptor for AGE) |  | 85 days |