Trial Outcomes & Findings for Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus (NCT NCT01447927)
NCT ID: NCT01447927
Last Updated: 2014-07-21
Results Overview
The percent change in pS6K1 was calculated as month 3 pS6k1 values minus baseline pS6k1 values, then divide by baseline pS6k1 values and multiply by 100.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
93 participants
Primary outcome timeframe
Baseline to 3 months
Results posted on
2014-07-21
Participant Flow
Ninety-three subjects were pre-registered through 12 Cancer Prevention Network (CPN) member organizations from February 2012 and January 2013.
One subject withdrew post-randomization and did not receive any treatment and 18 subjects were excluded from the trial before assignment to groups: 8 out of range lab values, 4 high grade dysplasia/esophagitis/esophageal stricture, 2 intestinal metaplasia on \<25% of biopsies, and 4 other reasons.
Participant milestones
| Measure |
Metformin
Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) on week 1, and twice daily (BID) on weeks 2-12 (every morning (QAM) every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression.
|
Placebo
Patients receive extended-release placebo orally (PO) once daily (QD) on week 1and BID on weeks 2-12 (every morning (QAM) and every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
36
|
|
Overall Study
COMPLETED
|
33
|
33
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
Metformin
Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) on week 1, and twice daily (BID) on weeks 2-12 (every morning (QAM) every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression.
|
Placebo
Patients receive extended-release placebo orally (PO) once daily (QD) on week 1and BID on weeks 2-12 (every morning (QAM) and every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus
Baseline characteristics by cohort
| Measure |
Metformin
n=38 Participants
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Placebo
n=36 Participants
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Total
n=74 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.5 years
n=5 Participants
|
60.5 years
n=7 Participants
|
60.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Performance Score
0-Fully active
|
37 participants
n=5 Participants
|
35 participants
n=7 Participants
|
72 participants
n=5 Participants
|
|
Performance Score
1-Ambulatory, restricted strenuous activity
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Body Mass Index
|
30.1 kg/m^2
n=5 Participants
|
29.9 kg/m^2
n=7 Participants
|
30.0 kg/m^2
n=5 Participants
|
|
Length of Barrett's segment
<5 cm of circumferential involvement
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Length of Barrett's segment
>=5 cm of circumferential involvement
|
27 participants
n=5 Participants
|
25 participants
n=7 Participants
|
52 participants
n=5 Participants
|
|
Non-steroidal anti-inflammatory drug (NSAID) use
Regular Use
|
9 participants
n=5 Participants
|
8 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Non-steroidal anti-inflammatory drug (NSAID) use
No Regular Use
|
29 participants
n=5 Participants
|
28 participants
n=7 Participants
|
57 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 3 monthsPopulation: Participants were considered evaluable for primary endpoint if pS6K1 data were available from both the pre- and post-intervention evaluations based on the intent-to-treat principle.
The percent change in pS6K1 was calculated as month 3 pS6k1 values minus baseline pS6k1 values, then divide by baseline pS6k1 values and multiply by 100.
Outcome measures
| Measure |
Metformin
n=36 Participants
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Placebo
n=33 Participants
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Percent Change in Median pS6K1 Immunostaining Among Participants With Barrett Esophagus
|
1.4 percentage of change
Full Range 157.1 • Interval -88.1 to 694.0
|
-14.7 percentage of change
Full Range 301.0 • Interval -97.7 to 1646.1
|
SECONDARY outcome
Timeframe: Up to 30 daysNumber of patients that experienced adverse events (grade 1 or above) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v. 4.0. The data reported in the table include only the commonly occurring adverse events (3 or more events).
Outcome measures
| Measure |
Metformin
n=38 Participants
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Placebo
n=36 Participants
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Overall Adverse Event Rates
Abdominal Pain
|
6 participants
|
0 participants
|
|
Overall Adverse Event Rates
Cough
|
0 participants
|
3 participants
|
|
Overall Adverse Event Rates
Dyspepsia
|
2 participants
|
3 participants
|
|
Overall Adverse Event Rates
Fatigue
|
4 participants
|
1 participants
|
|
Overall Adverse Event Rates
Flatulence
|
2 participants
|
2 participants
|
|
Overall Adverse Event Rates
Flu like symptoms
|
1 participants
|
2 participants
|
|
Overall Adverse Event Rates
Headache
|
3 participants
|
2 participants
|
|
Overall Adverse Event Rates
Nausea
|
5 participants
|
3 participants
|
|
Overall Adverse Event Rates
Diarrhea
|
10 participants
|
5 participants
|
|
Overall Adverse Event Rates
Gastrointestinal disorders - other, specify
|
2 participants
|
2 participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Metformin
Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=36 participants at risk
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Metformin
n=38 participants at risk
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Nervous system disorders
Amnesia
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
Other adverse events
| Measure |
Placebo
n=36 participants at risk
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
Metformin
n=38 participants at risk
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
2.8%
1/36 • Number of events 2
|
0.00%
0/38
|
|
Gastrointestinal disorders
Abdominal distension
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/36
|
15.8%
6/38 • Number of events 6
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
13.9%
5/36 • Number of events 7
|
26.3%
10/38 • Number of events 12
|
|
Gastrointestinal disorders
Dry mouth
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
3/36 • Number of events 3
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
2/36 • Number of events 2
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/36
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
5.6%
2/36 • Number of events 2
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Gastrointestinal disorders
Nausea
|
8.3%
3/36 • Number of events 3
|
13.2%
5/38 • Number of events 6
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
2/36 • Number of events 2
|
0.00%
0/38
|
|
General disorders
Chills
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
General disorders
Fatigue
|
2.8%
1/36 • Number of events 1
|
7.9%
3/38 • Number of events 4
|
|
General disorders
Flu like symptoms
|
5.6%
2/36 • Number of events 2
|
2.6%
1/38 • Number of events 1
|
|
General disorders
Localized edema
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Immune system disorders
Allergic reaction
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Infections and infestations
Sinusitis
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Infections and infestations
Tooth infection
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
|
Investigations
Creatinine increased
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Investigations
Weight loss
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify
|
2.8%
1/36 • Number of events 2
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Nervous system disorders
Dizziness
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Nervous system disorders
Headache
|
5.6%
2/36 • Number of events 2
|
7.9%
3/38 • Number of events 3
|
|
Nervous system disorders
Lethargy
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Nervous system disorders
Syncope
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Psychiatric disorders
Agitation
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/36
|
5.3%
2/38 • Number of events 2
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
3/36 • Number of events 3
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal mucositis
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
2.8%
1/36 • Number of events 1
|
2.6%
1/38 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
|
Vascular disorders
Flushing
|
2.8%
1/36 • Number of events 1
|
0.00%
0/38
|
|
Vascular disorders
Hypertension
|
0.00%
0/36
|
2.6%
1/38 • Number of events 1
|
Additional Information
Dr. Amitabh Chak
University Hospitals of Cleveland, Case Medical Center
Phone: 216-844-5385
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60