Metformin Hydrochloride in Treating Patients With Prostat... | NCT01433913

NCT01433913

Secondary IDs

ID	Type	Description	Link
NCI-2012-00243	Registry Identifier	CTRP (Clinical Trial Reporting Program)
CDR0000712087
UARIZ-UAZ10-16-01
11-0211-04	Other Identifier	Arizona Cancer Center - Tucson
UAZ10-16-01	Other Identifier	DCP
N01CN35158	U.S. NIH Grant/Contract		View source
P30CA023074	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I (metformin hydrochloride)	Experimental	Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.	Drug: metformin hydrochloride Other: laboratory biomarker analysis
Arm II (placebo)	Placebo Comparator	Patients receive placebo PO QD for 4-12 weeks.	Other: placebo Other: laboratory biomarker analysis

Name	Type	Description	Arm Group Labels	Other Names
metformin hydrochloride	Drug	Given PO	Arm I (metformin hydrochloride)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC)	Data between the two study groups will be compared using a two-group t-test at a two-sided 0.05 level of significance. If the data are not normally distributed, a non-parametric rank-sum test will be utilized.	12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry		12 weeks
Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3	Average number of positively stained cells that exhibited nuclear fragmentation from five randomly selected high-power fields (40x) in the tumor region was calculated for each participant

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Men will be eligible to this study if they are diagnosed with a histologically confirmed organ-confined adenocarcinoma of the prostate (PCa) treatable by prostatectomy and have a current PSA less than 50 ng/ml
Have not received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 5 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%)
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin =< 1.5 times institutional upper limits of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 times institutional ULN
Creatinine within normal institutional limits
Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Type I or type II diabetic patients on treatment with any drug for diabetes or participants with fasting glucose >= 126 mg/dL
History of impaired liver or kidney function
Participants with a current history of high alcohol consumption (> 3 standard drinks/day) or binge drinking (5 or more drinks) in one session of 1-3 hours
History of lactic acidosis or at increased risk for lactic acidosis such as patients with unstable or acute congestive heart failure who are at risk of hypoperfusion with hypoxemia
Participants may not be receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical composition to metformin
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
History of acute or chronic metabolic acidosis
Concurrent use of cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin)
Concurrent use of non-study metformin or other biguanides

Contacts/Locations Module

Name	Affiliation	Role
Robert Krouse	Arizona Cancer Center - Tucson	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Cancer Center - Tucson		Tucson	Arizona	85724-5024	United States
University of Arizona Health Sciences Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32994091	Derived	Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.
28692586	Derived	Nguyen MM, Martinez JA, Hsu CH, Sokoloff M, Krouse RS, Gibson BA, Nagle RB, Parnes HL, Cordova C, Chow HS. Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort. Eur J Cancer Prev. 2018 Nov;27(6):557-562. doi: 10.1097/CEJ.0000000000000394.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg metformin tablets until the day before surgery) for 4-12 weeks.
BG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets until the day before surgery) for 4-12 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00110 BG00220

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00065± 10 BG00161± 6 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00010 BG00110 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC)

Data between the two study groups will be compared using a two-group t-test at a two-sided 0.05 level of significance. If the data are not normally distributed, a non-parametric rank-sum test will be utilized.

Participants with tissue sections available from prostatectomy

Posted

Median

Inter-Quartile Range

% positively stained nuclei

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg metformin tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG0008 OG0019

Title

Denominators

Categories

Title	Measurements
	OG0006.5(3.33 to 9.33) OG0013.67(2 to 6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		0.23														Other

Secondary

Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry

analysis limited to patients with fresh frozen prostatectomy tissue

Posted

Median

Inter-Quartile Range

ug/g tissue

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3

Average number of positively stained cells that exhibited nuclear fragmentation from five randomly selected high-power fields (40x) in the tumor region was calculated for each participant

Participants with tissue sections available from prostatectomy

Posted

Median

Inter-Quartile Range

Number of positive cells

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants

Secondary

Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1

Participants with tissue sections available from prostatectomy

Posted

Median

Inter-Quartile Range

% positive cells

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K)

Participants with tissue sections available from prostatectomy

Posted

Median

Inter-Quartile Range

% positive cells

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34

Data were not collected due to budgetary constraints

Posted

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

AMPK Activation in the Prostatectomy Tissue as Assessed by IHC of p-AMPK

Data were not collected due to budgetary constraints

Posted

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Retinoblastoma Protein Phosphorylation (p-pRb)

Data were not collected due to budgetary constraints

Posted

12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum PSA

Analysis limited to participants with fasting serum samples

Posted

Median

Inter-Quartile Range

% change

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum Fasting Insulin

analysis limited to participants with fasting serum samples

Posted

Median

Inter-Quartile Range

% change

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum IGF-1/IGFBP-3

analysis limited to participants with fasting serum samples

Posted

Median

Inter-Quartile Range

% change

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum Testosterone

analysis limited to participants with fasting serum samples

Posted

Median

Inter-Quartile Range

% change

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum SHBG

analysis limited to participants with fasting serum samples

Posted

Median

Inter-Quartile Range

% change

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Secondary

Changes in Serum Fasting Glucose

Data were not collected because insulin is a more relevant outcome measure than glucose

Posted

Baseline and 12 weeks

ID	Title	Description
OG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD (one 500 mg metformin tablet daily for the first week, followed by two 500 mg metformin tablets daily for the second week, and then three 500 mg tablets daily until the day before surgery) for 4-12 weeks.
OG001	Arm II (Placebo)	Patients receive placebo PO QD (one placebo tablet daily for the first week, followed by two placebo tablets daily for the second week, and then three placebo tablets daily until the day before surgery) for 4-12 weeks.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I (Metformin Hydrochloride)	Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks. metformin hydrochloride: Given PO laboratory biomarker analysis: Correlative studies			1	10	6	10
EG001	Arm II (Placebo)	Patients receive placebo PO QD for 4-12 weeks. placebo: Given PO laboratory biomarker analysis: Correlative studies			0	10	5	10

Other Adverse Events

Term	Organ System	Statistical Information
Constipation	Gastrointestinal disorders	EG0001 affected10 at risk EG0010 affected10 at risk
Diarrhea	Gastrointestinal disorders	EG0002 affected10 at risk EG0010 affected10 at risk
Bloating	Gastrointestinal disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Nausea	Gastrointestinal disorders	EG0001 affected10 at risk EG0011 affected10 at risk
Diverticulosis	Gastrointestinal disorders	EG0001 affected10 at risk EG0010 affected10 at risk
Insomnia	Psychiatric disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Headache	Nervous system disorders	EG0001 affected10 at risk EG0011 affected10 at risk
Upper respiratory infection	Infections and infestations	EG0001 affected10 at risk EG0010 affected10 at risk
Chest pain	Cardiac disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Chest congestion	Respiratory, thoracic and mediastinal disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Urinary retention	Renal and urinary disorders	EG0001 affected10 at risk EG0011 affected10 at risk
Urinary urgency	Renal and urinary disorders	EG0001 affected10 at risk EG0010 affected10 at risk
Increased urinating frequency	Renal and urinary disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	EG0001 affected10 at risk EG0010 affected10 at risk
Backpain	Musculoskeletal and connective tissue disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	EG0001 affected10 at risk EG0010 affected10 at risk
Cough	Respiratory, thoracic and mediastinal disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Paresthesia	Nervous system disorders	EG0000 affected10 at risk EG0011 affected10 at risk
Sessile polyps in colon and rectum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0001 affected10 at risk EG0010 affected10 at risk
Pain	General disorders	EG0001 affected10 at risk EG0010 affected10 at risk

ID	Term
D011471	Prostatic Neoplasms

Ancestor Terms

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D008687	Metformin

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals