Trial Outcomes & Findings for Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer (NCT NCT01666730)
NCT ID: NCT01666730
Last Updated: 2021-08-10
Results Overview
Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Time from first day of treatment to death from any cause, assessed up to 1 year
Results posted on
2021-08-10
Participant Flow
Participant milestones
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
50
|
Reasons for withdrawal
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Study
Adverse Event
|
16
|
|
Overall Study
Death
|
2
|
|
Overall Study
Physician Decision
|
5
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Disease progression/relapse
|
18
|
Baseline Characteristics
Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from first day of treatment to death from any cause, assessed up to 1 yearCalculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Median Overall Survival (OS)
|
7.1 Months
Interval 5.0 to 9.2
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Patients that were evaluable for clinical response
CBR is the number of participants of the total analysis population who experience confirmed complete (CR) or partial response (PR) per RECIST CR = all detectable tumor has disappeared PR = a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum Stable Disease (SD) = small changes that do not meet previously given criteria. Progressive disease (PD) = a \>=20% increase in target lesions The true response rate of the combination therapy for this patient population will be estimated based on the number of response using a binomial distribution and its confidence intervals will be estimated using Wilson's method.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=31 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Response Rate (RR) Objective Tumor Response Based on Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans According to Response Evaluation Criteria in Solid Tumors (RECIST)
|
4 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Patients that were evaluable for clinical response
CBR is the number of participants of the total analysis population who experience a CR, PR, or SD per RECIST CR = all detectable tumor has disappeared PR = a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum SD = small changes that do not meet previously given criteria. PD = a \>=20% increase in target lesions
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=31 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Clinical Benefit Rate (CBR) Based on Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans According to RECIST
|
14 Participants
|
SECONDARY outcome
Timeframe: Time from first day of treatment received to the earlier documented disease progression or death from any cause, assessed up to 1 yearCalculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Progression Free Survival According to RECIST 1.1 Criteria
|
5.1 Months
Interval 1.8 to 6.6
|
SECONDARY outcome
Timeframe: Up to 1 yearThe toxicity profile of the combination will be tabulated.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 Participants
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Grade 3 and 4 Toxicities According to NCI CTCAE Version 4.0
Grade 3
|
60 Events
|
|
Number of Grade 3 and 4 Toxicities According to NCI CTCAE Version 4.0
Grade 4
|
2 Events
|
Adverse Events
Treatment (Metformin Hydrochloride, FOLFOX)
Serious events: 9 serious events
Other events: 33 other events
Deaths: 45 deaths
Serious adverse events
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 participants at risk
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Cardiac disorders
Chest pain - cardiac
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
General disorders
Death
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
General disorders
Edema limbs
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
General disorders
Fever
|
2.0%
1/50 • Number of events 2 • AEs will be collect up to 1 year
|
|
Hepatobiliary disorders
Bile duct stenosis
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Hepatobiliary disorders
Hepatobiliary disorder
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Infections and infestations
Infection- Klebsiella Bacteremia
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Infections and infestations
Mucosal infection
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Infections and infestations
Sepsis
|
2.0%
1/50 • Number of events 2 • AEs will be collect up to 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Injury, poisoning and procedural complications
Fracture
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Injury, poisoning and procedural complications
Head Injury
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
Blood bilirubin increased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
Creatinine increased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
Lymphocyte count decreased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
Neutrophil count decreased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
Platelet count decreased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Investigations
White blood cell decreased
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.0%
1/50 • Number of events 2 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death related to disease
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Nervous system disorders
Cognitive disturbance
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Vascular disorders
Hematoma
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Vascular disorders
Hypotension
|
4.0%
2/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Vascular disorders
Thromboembolic event
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
|
Vascular disorders
Pulmonary embolism
|
2.0%
1/50 • Number of events 1 • AEs will be collect up to 1 year
|
Other adverse events
| Measure |
Treatment (Metformin Hydrochloride, FOLFOX)
n=50 participants at risk
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
metformin hydrochloride: Given PO
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
48.0%
24/50 • Number of events 46 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
10/50 • Number of events 21 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Bloating
|
8.0%
4/50 • Number of events 4 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Constipation
|
26.0%
13/50 • Number of events 18 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
34.0%
17/50 • Number of events 32 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
6.0%
3/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
8.0%
4/50 • Number of events 4 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
12.0%
6/50 • Number of events 9 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
40.0%
20/50 • Number of events 35 • AEs will be collect up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
26.0%
13/50 • Number of events 18 • AEs will be collect up to 1 year
|
|
General disorders
Chills
|
8.0%
4/50 • Number of events 4 • AEs will be collect up to 1 year
|
|
General disorders
Edema limbs
|
14.0%
7/50 • Number of events 10 • AEs will be collect up to 1 year
|
|
General disorders
Fatigue
|
56.0%
28/50 • Number of events 59 • AEs will be collect up to 1 year
|
|
General disorders
Pain
|
10.0%
5/50 • Number of events 7 • AEs will be collect up to 1 year
|
|
Infections and infestations
Mucosal infection
|
6.0%
3/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Infections and infestations
Urinary tract infection
|
8.0%
4/50 • Number of events 9 • AEs will be collect up to 1 year
|
|
Injury, poisoning and procedural complications
Bruising
|
6.0%
3/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
8.0%
4/50 • Number of events 5 • AEs will be collect up to 1 year
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
10/50 • Number of events 12 • AEs will be collect up to 1 year
|
|
Investigations
Alkaline phosphatase increased
|
34.0%
17/50 • Number of events 32 • AEs will be collect up to 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
22.0%
11/50 • Number of events 19 • AEs will be collect up to 1 year
|
|
Investigations
Blood bilirubin increased
|
6.0%
3/50 • Number of events 4 • AEs will be collect up to 1 year
|
|
Investigations
Lymphocyte count decreased
|
32.0%
16/50 • Number of events 29 • AEs will be collect up to 1 year
|
|
Investigations
Neutrophil count decreased
|
24.0%
12/50 • Number of events 23 • AEs will be collect up to 1 year
|
|
Investigations
Platelet count decreased
|
34.0%
17/50 • Number of events 38 • AEs will be collect up to 1 year
|
|
Investigations
Weight loss
|
40.0%
20/50 • Number of events 32 • AEs will be collect up to 1 year
|
|
Investigations
White blood cell decreased
|
32.0%
16/50 • Number of events 24 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
12.0%
6/50 • Number of events 7 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
32.0%
16/50 • Number of events 30 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypernatremia
|
6.0%
3/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
36.0%
18/50 • Number of events 48 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
18.0%
9/50 • Number of events 28 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.0%
4/50 • Number of events 5 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
26.0%
13/50 • Number of events 26 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
16.0%
8/50 • Number of events 10 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
20.0%
10/50 • Number of events 16 • AEs will be collect up to 1 year
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
6.0%
3/50 • Number of events 5 • AEs will be collect up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.0%
4/50 • Number of events 4 • AEs will be collect up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
18.0%
9/50 • Number of events 10 • AEs will be collect up to 1 year
|
|
Nervous system disorders
Dizziness
|
14.0%
7/50 • Number of events 8 • AEs will be collect up to 1 year
|
|
Nervous system disorders
Dysgeusia
|
16.0%
8/50 • Number of events 12 • AEs will be collect up to 1 year
|
|
Nervous system disorders
Paresthesia
|
10.0%
5/50 • Number of events 5 • AEs will be collect up to 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
10/50 • Number of events 21 • AEs will be collect up to 1 year
|
|
Psychiatric disorders
Anxiety
|
16.0%
8/50 • Number of events 8 • AEs will be collect up to 1 year
|
|
Psychiatric disorders
Depression
|
10.0%
5/50 • Number of events 6 • AEs will be collect up to 1 year
|
|
Psychiatric disorders
Insomnia
|
20.0%
10/50 • Number of events 10 • AEs will be collect up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.0%
8/50 • Number of events 10 • AEs will be collect up to 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
22.0%
11/50 • Number of events 11 • AEs will be collect up to 1 year
|
|
Vascular disorders
Hot flashes
|
6.0%
3/50 • Number of events 3 • AEs will be collect up to 1 year
|
|
Vascular disorders
Hypertension
|
28.0%
14/50 • Number of events 18 • AEs will be collect up to 1 year
|
Additional Information
Dr. David Bajor
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Phone: 1-800-641-2422
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place