Study of Metformin Plus Oligomeric Procyanidin Complex for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients

NCT03465345 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 102797
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this study is to identify a safe dose of metformin, in combination with oligomeric procyanidin complex (OPC) for pharmacologic reduction of AGE levels in patients with prostate cancer.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of metformin in combination with OPC in PCa subjects.

  112 days

Secondary Outcomes (11)

• Correlation between changes to AGE level and changes to PSA.

  112 days

• Correlation between changes to AGE level and changes to BMI.

  112 days

• Correlation between changes to AGE level and changes to insulin resistance.

  112 days

• Correlation between changes to AGE level and changes to A1C.

  112 days

• Correlations between changes to AGE level and changes to testosterone.

  112 days

Study Arms (1)

Metformin + OPC dose escalation

EXPERIMENTAL

Drug: Metformin; Drug: Oligomeric Procyanidin Complex

Interventions

Metformin DRUG

Metformin: The starting dose for Metformin is 850mg once a day, the second dose is 850mg once a day; the third dose level is 850mg twice a day; the fourth dose level is 850mg twice a day. Each dose level lasts for 28 days.

Metformin + OPC dose escalation

Oligomeric Procyanidin Complex DRUG

OPC: The starting dose for OPC is 500mg once a day; the second dose is 1000mg once a day; the third dose level is 1000mg once a day; the fourth dose level is 1500mg once a day. Each dose level lasts for 28 days.

Also known as: OPC

Metformin + OPC dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 Cockkroft and Gault formula (see appendix C).
• Liver Function: Total bilirubin ≤ULN, AST and ALT \<1.5xULN, Prior radiation therapy allowed
• Subjects may have diabetes mellitus but must not be taking metformin.
• Able to swallow and retain oral medication
• ECOG performance status of 0 - 2
• Ability to sign written informed consent
• Testosterone level \<50ng/dL at time of enrollment.
• Age 18 or older.

You may not qualify if:

• Known allergy to grapes or grape seed
• Known hypersensitivity or intolerance to metformin.
• Any condition associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heart failure defined as NYHA Class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day).
• Prior cytotoxic chemotherapy for metastatic prostate cancer; prior treatment with genomically-targeted agents, or Provenge is allowed.
• History of receiving more than 2 classes of ADT.
• Current use of metformin, or 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
• PSA doubling time of \<6 months, measured over the 3 months prior to enrollment.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Michael Lilly, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2018
• First Posted: March 14, 2018
• Study Start: July 11, 2018
• Primary Completion: July 11, 2018
• Study Completion: July 11, 2018
• Last Updated: August 3, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)