Trial Outcomes & Findings for Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI (NCT NCT01312467)

Last Updated: 2019-03-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

From baseline to 12 weeks

Results posted on

2019-03-05

Participant Flow

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).

Participant milestones

Participant milestones
Measure	Prevention (Metformin Hydrochloride) 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 Study STARTED	45
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Prevention (Metformin Hydrochloride) 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 Study Adverse Event	4
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	2
Overall Study Deported to country of origin	1
Overall Study Another medical condition	1
Overall Study Ineligible	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prevention (Metformin Hydrochloride) n=45 Participants 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
Age, Continuous	59.6 years STANDARD_DEVIATION 6.83 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Region of Enrollment United States	45 participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to 12 weeks

Population: The analysis is based on 32 participants who have evaluable data.

Outcome measures

Outcome measures
Measure	Prevention (Metformin Hydrochloride) n=32 Participants 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
Change in Activated S6serine235 (i.e., the Ratio of pS6serine235/S6serine235)	0.0228 weighted ratio of staining cells Standard Deviation 0.444

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: Funding was not secured to complete the secondary and tertiary endpoints.

Data not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: Funding was not secured to complete the secondary and tertiary endpoints.

Data not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: 45 participants were enrolled and 45 participants were analyzed for toxicity.

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.

Outcome measures

Outcome measures
Measure	Prevention (Metformin Hydrochloride) n=45 Participants 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
Safety and Tolerability of Metformin Hydrochloride Treatment Grade 1	186 adverse events
Safety and Tolerability of Metformin Hydrochloride Treatment Grade 2	23 adverse events
Safety and Tolerability of Metformin Hydrochloride Treatment Grade 3 or higher	1 adverse events

Adverse Events

Prevention (Metformin Hydrochloride)

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Prevention (Metformin Hydrochloride) n=45 participants at risk 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
Reproductive system and breast disorders DUCTAL CARCINOMA IN SITU, HIGH GRADE, SOLID AND CRIBRIFORM TYPE WITH APOCRINE FEATURES AND FOCAL NEC	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).

Other adverse events

Other adverse events
Measure	Prevention (Metformin Hydrochloride) n=45 participants at risk 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
Gastrointestinal disorders ABDOMINAL CRAMPING	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders ABDOMINAL PAIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders BACK PAIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders BLOATING	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Infections and infestations COLD	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders CONSTIPATION	11.1% 5/45 • Number of events 5 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Respiratory, thoracic and mediastinal disorders COUGH	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders CRAMPING	6.7% 3/45 • Number of events 8 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders CRAMPS IN LEGS	2.2% 1/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Ear and labyrinth disorders DECREASED HEARING	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders DIARRHEA	31.1% 14/45 • Number of events 25 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Renal and urinary disorders DIFFICULTY HOLDING BLADDER-URGENCY	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders DIZZINESS	15.6% 7/45 • Number of events 7 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders DRY MOUTH	6.7% 3/45 • Number of events 3 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Skin and subcutaneous tissue disorders DRY SKIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders ELEVATED TEMPERATURE	2.2% 1/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Eye disorders EYE IRRITATION	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders FATIGUE	15.6% 7/45 • Number of events 7 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Psychiatric disorders FEELS AWAKE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders FELT COLD	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders FEVER	4.4% 2/45 • Number of events 3 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders FLATULENCE	17.8% 8/45 • Number of events 8 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders HEADACHE	11.1% 5/45 • Number of events 5 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders HEARTBURN	11.1% 5/45 • Number of events 6 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Skin and subcutaneous tissue disorders HEAT RASH	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders HEEL PAIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders HEMATOCHEZIA	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Blood and lymphatic system disorders HEMATOCRIT LAB RESULT BELOW THE NORMAL RANGE	2.2% 1/45 • Number of events 4 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Blood and lymphatic system disorders HEMOGLOBIN LAB RESULT BELOW THE NORMAL RANGE	2.2% 1/45 • Number of events 4 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders HEMORRHOIDS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Vascular disorders HYPERTENSION	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders HYPOGLYCEMIA	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders HYPOGLYCEMIC	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders INCREASED APPETITE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders INCREASED GAS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Skin and subcutaneous tissue disorders INCREASED SWEATING	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Infections and infestations INFECTION IN SITE OF LUMPECTOMY	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Psychiatric disorders INSOMNIA	6.7% 3/45 • Number of events 3 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Blood and lymphatic system disorders IRON LAB RESULT OUT OF RANGE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Skin and subcutaneous tissue disorders ITCHY SKIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Respiratory, thoracic and mediastinal disorders ITCHY THROAT	2.2% 1/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders JITTERS	2.2% 1/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders KNEE PAIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders LEG CRAMPS	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders LIGHTHEADED	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders LIGHTHEADED/DIZZINESS	2.2% 1/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Nervous system disorders LIGHTHEADEDNESS	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders LOOSE STOOLS	8.9% 4/45 • Number of events 4 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders LOOSE STOOLS/DIARRHEA	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders LOSS OF APPETITE	13.3% 6/45 • Number of events 6 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders LOSS OF APPETITE-EATING LESS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders MILD CRAMPING	4.4% 2/45 • Number of events 5 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders MILD GERD	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Injury, poisoning and procedural complications MORE BRUISING	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders MUSCLE PAIN	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Infections and infestations NASAL CONGESTION	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders NAUSEA	15.6% 7/45 • Number of events 8 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders SCIATICA FLARE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Eye disorders SCRATCHED LEFT EYE CORNEA	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Respiratory, thoracic and mediastinal disorders SHORTNESS OF BREATH	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders SLIGHT COLD	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders SMALLER APPETITE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders SORE RIGHT WRIST	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders STOMACH CRAMPS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders STOMACH DISCOMFORT	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders STOMACH PAIN	13.3% 6/45 • Number of events 7 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Respiratory, thoracic and mediastinal disorders STUFFY NOSE	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Skin and subcutaneous tissue disorders SWEATING	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Metabolism and nutrition disorders SWEET CRAVINGS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
General disorders SWELLING LESS IN FEET	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Blood and lymphatic system disorders TRANSFERRIN SATURATION OUT OF RANGE - LOW	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Musculoskeletal and connective tissue disorders TWITCHING RIGHT THIGH	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders VERY LOOSE STOOLS	2.2% 1/45 • Number of events 1 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).
Gastrointestinal disorders VOMITING	4.4% 2/45 • Number of events 2 • Adverse Events that were occurred on and after the treatment began date to the end of the study (up to 16 weeks).

Additional Information

Dr. Frank L. Meyskens, Jr.

University of California, Irvine

Phone: 714-456-6310

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60