Trial Outcomes & Findings for Nivolumab and Metformin in Patients With Treatment Refractory MSS Colorectal Cancer (NCT NCT03800602)
NCT ID: NCT03800602
Last Updated: 2024-09-05
Results Overview
Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1., and rate will be calculated as a proportion (responders/total patients).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
29 participants
Primary outcome timeframe
Up to 1 year after study start
Results posted on
2024-09-05
Participant Flow
Participant milestones
| Measure |
Treatment (Nivolumab, Metformin)
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Overall Study
STARTED
|
29
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab and Metformin in Patients With Treatment Refractory MSS Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Nivolumab, Metformin)
n=24 Participants
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
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
|
5 Participants
n=5 Participants
|
|
Age, Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 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
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 1 year after study startPopulation: 6 patients were replaced per protocol, and 18 patients had evaluable disease.
Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1., and rate will be calculated as a proportion (responders/total patients).
Outcome measures
| Measure |
Treatment (Nivolumab, Metformin)
n=18 Participants
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Overall Response Rate (ORR)
Stable Disease
|
2 Participants
|
|
Overall Response Rate (ORR)
Progressive Disease
|
16 Participants
|
SECONDARY outcome
Timeframe: Assessed up to 2 years after study startPopulation: 6 patients were replaced per protocol, and 18 patients had evaluable disease.
For progression free survival, progression or death from any cause will be defined as the event. Patients will be censored at time of last follow-up.
Outcome measures
| Measure |
Treatment (Nivolumab, Metformin)
n=18 Participants
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Progression Free Survival (PFS)
|
2.3 months
Interval 1.7 to 2.3
|
SECONDARY outcome
Timeframe: Assessed up to 2 years after study startPopulation: 6 patients were replaced per protocol, and 18 patients had evaluable disease.
For overall survival, death from any cause will be defined as the event. Patients will be censored at time of last follow-up.
Outcome measures
| Measure |
Treatment (Nivolumab, Metformin)
n=18 Participants
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Overall Survival (OS)
|
5.2 months
Interval 3.2 to 11.7
|
SECONDARY outcome
Timeframe: Up to 1 year after study startPopulation: This outcome was not analyzed because the data were not collected.
Tumor marker carcinoembryonic antigen (CEA) will be assessed.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Nivolumab, Metformin)
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment (Nivolumab, Metformin)
n=18 participants at risk
Patients receive metformin PO BID starting on day 1. After 14 days of metformin only period patients also receive nivolumab IV every 4 weeks starting on day 15. Courses repeat every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity or consent withdrawal.
Metformin: Given PO
Nivolumab: Given IV
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
55.6%
10/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Nausea
|
33.3%
6/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Abdominal Pain
|
27.8%
5/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Vomiting
|
27.8%
5/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Fatigue
|
27.8%
5/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
3/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
3/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Fever
|
16.7%
3/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Metabolism and nutrition disorders
Weight Loss
|
16.7%
3/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Abdominal Distension
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Psychiatric disorders
Anxiety
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Ast Increased
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Constipation
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Metabolism and nutrition disorders
Dehydration
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Musculoskeletal and connective tissue disorders
Lower Back Pain
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Pelvic Pain
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Respiratory, thoracic and mediastinal disorders
Shortness Of Breath
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Abdominal Cramps
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Alk Phos Increased
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Vascular disorders
B/L Le Edema
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Bloating
|
5.6%
1/18 • Number of events 1 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Blood in Ostomy
|
5.6%
1/18 • Number of events 1 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Cardiac disorders
Chest Pain
|
5.6%
1/18 • Number of events 1 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Clostridioides Difficile Colitis
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Decreased Appetite
|
16.7%
3/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Dyphasia
|
5.6%
1/18 • Number of events 1 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Elevated Ldh
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Hyperbilirubinemia
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Hyperhidrosis (Night Sweats)
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Hypoalbuminemia
|
11.1%
2/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Hypokalemia
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Musculoskeletal and connective tissue disorders
Left Hip Pain
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Renal and urinary disorders
Left Hydronephrosis
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Endocrine disorders
Liver Failure
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Lle Dvt
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Renal and urinary disorders
Loss Of Bladder Control
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Loss Of Taste
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Lower Extremity Swelling
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Lymphocyte Count Decreased
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Skin and subcutaneous tissue disorders
Mouth Lesion
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Neck Pain
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
General disorders
Netropenia
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Skin and subcutaneous tissue disorders
Pain At Biopsy Site
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Pain Lower Abdomen
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Blood and lymphatic system disorders
Pulmonary Emoblism
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Skin and subcutaneous tissue disorders
Rash Underbreast
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Renal and urinary disorders
Rectal Discharge
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Rectal Obstruction
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Gastrointestinal disorders
Rectal Pain
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Eye disorders
Right Droopy Eye
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Injury, poisoning and procedural complications
Right Internal Juglar Vein Thrombus
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Infections and infestations
Sepsis
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Skin and subcutaneous tissue disorders
Skin Itching
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Musculoskeletal and connective tissue disorders
Upper Back Pain
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.6%
1/18 • Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Month 12.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place