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Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01312467
Recruitment Status : Completed
First Posted : March 10, 2011
Results First Posted : June 25, 2015
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Adenomatous Polyp
Colorectal Cancer
Obesity
Intervention Drug: metformin hydrochloride
Enrollment 45
Recruitment Details Between 2011 and 2013, 45 obese colorectal adenoma (CRA) patients were enrolled at three study sites: UC Irvine, Long Beach VAMC, and Kaiser Permanente, Sacramento).
Pre-assignment Details  
Arm/Group Title Prevention (Metformin Hydrochloride)
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Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride: Given PO

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Period Title: Overall Study
Started 45
Completed 32
Not Completed 13
Reason Not Completed
Adverse Event             4
Lost to Follow-up             1
Withdrawal by Subject             2
Deported to country of origin             1
Another medical condition             1
Ineligible             4
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride: Given PO

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Overall Number of Baseline Participants 45
Hide Baseline Analysis Population Description
45 participants were enrolled into the study
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants
59.6  (6.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Female
15
  33.3%
Male
30
  66.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 45 participants
45
1.Primary Outcome
Title Change in Activated S6serine235 (i.e., the Ratio of pS6serine235/S6serine235)
Hide Description Tissue S6Ser235 immunostaining was analyzed by the study pathologist using Histo Score (HScore) analysis at baseline and post- metformin (Week 12). The Hscore is determined by estimation of the percentage of cells positively stained with mild, moderate, or strong staining intensity. The final score is determined by weighted estimate, as follows: Hscore = (# cell stained with High intensity/total # cells)x3 + (# cells stained with median intensity/total # cells)x2 + (# cells stained with low intensity/total # cells)x1. Mean and standard deviation of the change in the histo score (H score) of pS6serine235 from baseline were calcuated.
Time Frame From baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is based on 32 participants who have evaluable data.
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description:

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride: Given PO

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: weighted ratio of staining cells
0.0228  (0.444)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prevention (Metformin Hydrochloride)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > 0.773
Comments [Not Specified]
Method A paired t-test
Comments [Not Specified]
2.Secondary Outcome
Title Effects of Metformin Hydrochloride on Colorectal Mucosa Proliferation (Ki-67, Phosphorylated IGF-1 Receptor, Phosphorylated Insulin Receptor, Phosphorylated AKT, Phosphorylated mTOR, and Phosphorylated AMP Kinase)
Hide Description Data not collected.
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Funding was not secured to complete the secondary and tertiary endpoints.
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description:

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Effects of Metformin Hydrochloride on Serum (Fasting and 2 Hour Postprandial Insulin and Glucose, Fasting IGF-1, IGFBP-1, IGFBP-3, Leptin, Adiponectin and Metformin Levels)
Hide Description Data not collected.
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Funding was not secured to complete the secondary and tertiary endpoints.
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description:

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Safety and Tolerability of Metformin Hydrochloride Treatment
Hide Description All participants will be evaluable for toxicity from the time of their first dose of metformin. Since toxicities in this study are measured as categorical data, primary analysis shall be by tests of binomial proportions (e.g., Mantel-Haenszel chi-squared statistic). This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0 for toxicity and Serious Adverse Event reporting.
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
45 participants were enrolled and 45 participants were analyzed for toxicity.
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description:

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride

Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: adverse events
Grade 1 186
Grade 2 23
Grade 3 or higher 1
Time Frame Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prevention (Metformin Hydrochloride)
Hide Arm/Group Description

Patients receive metformin hydrochloride PO QD during week 1 and then BID during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

metformin hydrochloride: Given PO

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

All-Cause Mortality
Prevention (Metformin Hydrochloride)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prevention (Metformin Hydrochloride)
Affected / at Risk (%) # Events
Total   1/45 (2.22%)    
Reproductive system and breast disorders   
DUCTAL CARCINOMA IN SITU, HIGH GRADE, SOLID AND CRIBRIFORM TYPE WITH APOCRINE FEATURES AND FOCAL NEC * 1  1/45 (2.22%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Prevention (Metformin Hydrochloride)
Affected / at Risk (%) # Events
Total   36/45 (80.00%)    
Blood and lymphatic system disorders   
HEMATOCRIT LAB RESULT BELOW THE NORMAL RANGE * 1  1/45 (2.22%)  4
HEMOGLOBIN LAB RESULT BELOW THE NORMAL RANGE * 1  1/45 (2.22%)  4
IRON LAB RESULT OUT OF RANGE * 1  1/45 (2.22%)  1
TRANSFERRIN SATURATION OUT OF RANGE – LOW * 1  1/45 (2.22%)  1
Ear and labyrinth disorders   
DECREASED HEARING * 1  1/45 (2.22%)  1
Eye disorders   
EYE IRRITATION * 1  1/45 (2.22%)  1
SCRATCHED LEFT EYE CORNEA * 1  1/45 (2.22%)  1
Gastrointestinal disorders   
ABDOMINAL CRAMPING * 1  1/45 (2.22%)  1
ABDOMINAL PAIN * 1  1/45 (2.22%)  1
BLOATING * 1  1/45 (2.22%)  1
CONSTIPATION * 1  5/45 (11.11%)  5
CRAMPING * 1  3/45 (6.67%)  8
DIARRHEA * 1  14/45 (31.11%)  25
DRY MOUTH * 1  3/45 (6.67%)  3
FLATULENCE * 1  8/45 (17.78%)  8
HEARTBURN * 1  5/45 (11.11%)  6
HEMATOCHEZIA * 1  1/45 (2.22%)  1
HEMORRHOIDS * 1  1/45 (2.22%)  1
INCREASED GAS * 1  1/45 (2.22%)  1
LOOSE STOOLS * 1  4/45 (8.89%)  4
LOOSE STOOLS/DIARRHEA * 1  1/45 (2.22%)  1
MILD CRAMPING * 1  2/45 (4.44%)  5
MILD GERD * 1  1/45 (2.22%)  1
NAUSEA * 1  7/45 (15.56%)  8
STOMACH CRAMPS * 1  1/45 (2.22%)  1
STOMACH DISCOMFORT * 1  1/45 (2.22%)  1
STOMACH PAIN * 1  6/45 (13.33%)  7
VERY LOOSE STOOLS * 1  1/45 (2.22%)  1
VOMITING * 1  2/45 (4.44%)  2
General disorders   
ELEVATED TEMPERATURE * 1  1/45 (2.22%)  2
FATIGUE * 1  7/45 (15.56%)  7
FELT COLD * 1  1/45 (2.22%)  1
FEVER * 1  2/45 (4.44%)  3
SLIGHT COLD * 1  1/45 (2.22%)  1
SWELLING LESS IN FEET * 1  1/45 (2.22%)  1
Infections and infestations   
COLD * 1  1/45 (2.22%)  1
INFECTION IN SITE OF LUMPECTOMY * 1  1/45 (2.22%)  1
NASAL CONGESTION * 1  1/45 (2.22%)  1
Injury, poisoning and procedural complications   
MORE BRUISING * 1  1/45 (2.22%)  1
Metabolism and nutrition disorders   
HYPOGLYCEMIA * 1  1/45 (2.22%)  1
HYPOGLYCEMIC * 1  1/45 (2.22%)  1
INCREASED APPETITE * 1  1/45 (2.22%)  1
LOSS OF APPETITE * 1  6/45 (13.33%)  6
LOSS OF APPETITE-EATING LESS * 1  1/45 (2.22%)  1
SMALLER APPETITE * 1  1/45 (2.22%)  1
SWEET CRAVINGS * 1  1/45 (2.22%)  1
Musculoskeletal and connective tissue disorders   
BACK PAIN * 1  1/45 (2.22%)  1
CRAMPS IN LEGS * 1  1/45 (2.22%)  2
HEEL PAIN * 1  1/45 (2.22%)  1
KNEE PAIN * 1  1/45 (2.22%)  1
LEG CRAMPS * 1  2/45 (4.44%)  2
MUSCLE PAIN * 1  1/45 (2.22%)  1
SCIATICA FLARE * 1  1/45 (2.22%)  1
SORE RIGHT WRIST * 1  1/45 (2.22%)  1
TWITCHING RIGHT THIGH * 1  1/45 (2.22%)  1
Nervous system disorders   
DIZZINESS * 1  7/45 (15.56%)  7
HEADACHE * 1  5/45 (11.11%)  5
JITTERS * 1  1/45 (2.22%)  2
LIGHTHEADED * 1  2/45 (4.44%)  2
LIGHTHEADED/DIZZINESS * 1  1/45 (2.22%)  2
LIGHTHEADEDNESS * 1  2/45 (4.44%)  2
Psychiatric disorders   
FEELS AWAKE * 1  1/45 (2.22%)  1
INSOMNIA * 1  3/45 (6.67%)  3
Renal and urinary disorders   
DIFFICULTY HOLDING BLADDER-URGENCY * 1  1/45 (2.22%)  1
Respiratory, thoracic and mediastinal disorders   
COUGH * 1  1/45 (2.22%)  1
ITCHY THROAT * 1  1/45 (2.22%)  2
SHORTNESS OF BREATH * 1  2/45 (4.44%)  2
STUFFY NOSE * 1  1/45 (2.22%)  1
Skin and subcutaneous tissue disorders   
DRY SKIN * 1  1/45 (2.22%)  1
HEAT RASH * 1  1/45 (2.22%)  1
INCREASED SWEATING * 1  1/45 (2.22%)  1
ITCHY SKIN * 1  1/45 (2.22%)  1
SWEATING * 1  2/45 (4.44%)  2
Vascular disorders   
HYPERTENSION * 1  1/45 (2.22%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Frank L. Meyskens, Jr.
Organization: University of California, Irvine
Phone: 714-456-6310
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01312467     History of Changes
Other Study ID Numbers: NCI-2011-01744
NCI-2011-01744 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
UCI 10-31 ( Other Identifier: Chao Family Comprehensive Cancer Center )
2010-7705 ( Other Identifier: UCIrvine )
UCI09-13-01 ( Other Identifier: DCP )
P30CA062203 ( U.S. NIH Grant/Contract )
N01CN35160 ( U.S. NIH Grant/Contract )
First Submitted: March 7, 2011
First Posted: March 10, 2011
Results First Submitted: May 11, 2015
Results First Posted: June 25, 2015
Last Update Posted: March 5, 2019