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

Primary Purpose

Prostate Cancer

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Metformin

Oligomeric Procyanidin Complex

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.
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.

Exclusion Criteria:

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.

Sites / Locations

Medical University of South Carolina

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Metformin + OPC dose escalation

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Correlation between changes to AGE level and changes to PSA.

Correlation between changes to AGE level and changes to BMI.

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

Correlation between changes to AGE level and changes to A1C.

Correlations between changes to AGE level and changes to testosterone.

Correlation between changes to AGE level and changes to diet.

Correlation between changes to AGE level and changes to quality of life.

FACT-P and AUA questionnaires

Frequency of adverse events as assessed by CTCAE v. 4

Toxicities will be tabulated 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.

Correlation between AGE levels and sRAGE (soluble receptor for AGE) expression and signaling.

Correlation between changes to AGE level and OPC metabolite levels.

Correlation between changes to AGE level and changes in the stool. microbiome.

Full Information

NCT ID

NCT03465345

First Posted

February 27, 2018

Last Updated

August 1, 2018

Sponsor

Medical University of South Carolina

1. Study Identification

Unique Protocol Identification Number

NCT03465345

Brief Title

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

Official Title

Phase 1b Study of Metformin Plus Oligomeric Procyanidin Complex for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Study was stopped to pursue a new treatment plan with a new study.

Study Start Date

July 11, 2018 (Actual)

Primary Completion Date

July 11, 2018 (Actual)

Study Completion Date

July 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Medical University of South Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

AGEs (advanced glycation endpoints) 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 identify safe pharmaceutical agents that can reduce the AGE levels in subjects with advanced cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin + OPC dose escalation

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oligomeric Procyanidin Complex

Other Intervention Name(s)

OPC

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

112 days

Secondary Outcome Measure Information:

Title

Correlation between changes to AGE level and changes to PSA.

Time Frame

112 days

Title

Correlation between changes to AGE level and changes to BMI.

Time Frame

112 days

Title

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

Time Frame

112 days

Title

Correlation between changes to AGE level and changes to A1C.

Time Frame

112 days

Title

Correlations between changes to AGE level and changes to testosterone.

Time Frame

112 days

Title

Correlation between changes to AGE level and changes to diet.

Time Frame

112 days

Title

Correlation between changes to AGE level and changes to quality of life.

Description

FACT-P and AUA questionnaires

Time Frame

112 days

Title

Frequency of adverse events as assessed by CTCAE v. 4

Description

Toxicities will be tabulated 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.

Time Frame

112 days

Title

Correlation between AGE levels and sRAGE (soluble receptor for AGE) expression and signaling.

Time Frame

112 days

Title

Correlation between changes to AGE level and OPC metabolite levels.

Time Frame

112 days

Title

Correlation between changes to AGE level and changes in the stool. microbiome.

Time Frame

112 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Lilly, MD

Organizational Affiliation

Medical University of South Carolina

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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