Trial Outcomes & Findings for Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery (NCT NCT01433913)
NCT ID: NCT01433913
Last Updated: 2018-01-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
12 weeks
Results posted on
2018-01-10
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
9
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery
Baseline characteristics by cohort
| Measure |
Arm I (Metformin Hydrochloride)
n=10 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Continuous
|
65 years
STANDARD_DEVIATION 10 • n=5 Participants
|
61 years
STANDARD_DEVIATION 6 • n=7 Participants
|
63 years
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Participants with tissue sections available from prostatectomy
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.
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=9 Participants
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.
|
|---|---|---|
|
Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC)
|
6.5 % positively stained nuclei
Interval 3.33 to 9.33
|
3.67 % positively stained nuclei
Interval 2.0 to 6.0
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: analysis limited to patients with fresh frozen prostatectomy tissue
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=7 Participants
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.
|
|---|---|---|
|
Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry
|
5.71 ug/g tissue
Interval 2.62 to 16.18
|
0 ug/g tissue
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants with tissue sections available from prostatectomy
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
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=9 Participants
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.
|
|---|---|---|
|
Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3
|
0.07 Number of positive cells
Interval 0.0 to 0.27
|
0.1 Number of positive cells
Interval 0.0 to 0.27
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants with tissue sections available from prostatectomy
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=9 Participants
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.
|
|---|---|---|
|
Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1
|
37.5 % positive cells
Interval 20.83 to 59.17
|
13.3 % positive cells
Interval 6.7 to 21.7
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants with tissue sections available from prostatectomy
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=9 Participants
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.
|
|---|---|---|
|
mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K)
|
66.7 % positive cells
Interval 36.67 to 88.33
|
63.3 % positive cells
Interval 39.2 to 80.0
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Data were not collected due to budgetary constraints
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksPopulation: Data were not collected due to budgetary constraints
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 weeksPopulation: Data were not collected due to budgetary constraints
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: Analysis limited to participants with fasting serum samples
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
|---|---|---|
|
Changes in Serum PSA
|
-6.53 % change
Interval -9.45 to 16.76
|
5.98 % change
Interval -6.91 to 22.98
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: analysis limited to participants with fasting serum samples
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
|---|---|---|
|
Changes in Serum Fasting Insulin
|
-11.42 % change
Interval -33.26 to 16.88
|
5.66 % change
Interval -10.67 to 22.47
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: analysis limited to participants with fasting serum samples
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
|---|---|---|
|
Changes in Serum IGF-1/IGFBP-3
|
7.07 % change
Interval -8.51 to 21.77
|
-2.24 % change
Interval -18.2 to 25.71
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: analysis limited to participants with fasting serum samples
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
|---|---|---|
|
Changes in Serum Testosterone
|
-16.12 % change
Interval -20.43 to 3.1
|
2.04 % change
Interval -16.7 to 28.77
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: analysis limited to participants with fasting serum samples
Outcome measures
| Measure |
Arm I (Metformin Hydrochloride)
n=8 Participants
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.
|
Arm II (Placebo)
n=10 Participants
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.
|
|---|---|---|
|
Changes in Serum SHBG
|
0.48 % change
Interval -6.64 to 7.19
|
-6.49 % change
Interval -12.43 to 4.33
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksPopulation: Data were not collected because insulin is a more relevant outcome measure than glucose
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Metformin Hydrochloride)
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Arm II (Placebo)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm I (Metformin Hydrochloride)
n=10 participants at risk
Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
metformin hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Placebo)
n=10 participants at risk
Patients receive placebo PO QD for 4-12 weeks.
placebo: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Infections and infestations
influenza
|
10.0%
1/10
|
0.00%
0/10
|
Other adverse events
| Measure |
Arm I (Metformin Hydrochloride)
n=10 participants at risk
Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
metformin hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Placebo)
n=10 participants at risk
Patients receive placebo PO QD for 4-12 weeks.
placebo: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
10.0%
1/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
2/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10
|
10.0%
1/10
|
|
Gastrointestinal disorders
Diverticulosis
|
10.0%
1/10
|
0.00%
0/10
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/10
|
10.0%
1/10
|
|
Nervous system disorders
Headache
|
10.0%
1/10
|
10.0%
1/10
|
|
Infections and infestations
Upper respiratory infection
|
10.0%
1/10
|
0.00%
0/10
|
|
Cardiac disorders
Chest pain
|
0.00%
0/10
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Chest congestion
|
0.00%
0/10
|
10.0%
1/10
|
|
Renal and urinary disorders
Urinary retention
|
10.0%
1/10
|
10.0%
1/10
|
|
Renal and urinary disorders
Urinary urgency
|
10.0%
1/10
|
0.00%
0/10
|
|
Renal and urinary disorders
Increased urinating frequency
|
0.00%
0/10
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
1/10
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Backpain
|
0.00%
0/10
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
10.0%
1/10
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/10
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/10
|
10.0%
1/10
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/10
|
10.0%
1/10
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Sessile polyps in colon and rectum
|
10.0%
1/10
|
0.00%
0/10
|
|
General disorders
Pain
|
10.0%
1/10
|
0.00%
0/10
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60