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Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma

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: NCT01479465
Recruitment Status : Terminated
First Posted : November 24, 2011
Results First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Biological: Simtuzumab
Drug: Placebo to match SIM
Drug: Leucovorin
Drug: Irinotecan
Drug: Fluorouracil
Enrollment 266
Recruitment Details Participants were enrolled at study sites in the United States, Russia, and Europe. The first participant was screened on 15 December 2011. The last study visit occurred on 27 February 2015.
Pre-assignment Details 358 participants were screened.
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Hide Arm/Group Description Participants received simtuzumab (SIM) 700 mg via intravenous infusion followed by leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI; l-leucovorin 200 mg/m^2 or dl-leucovorin 400 mg/m^2 administered via intravenous infusion over 2 hours and irinotecan 180 mg/m^2 administered via intravenous infusion over 90 minutes, followed by fluorouracil 400 mg/m^2 administered via intravenous bolus and 2400 mg/m^2 via intravenous infusion over 46 hours) on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
Period Title: Overall Study
Started 11 84 86 85
Completed 0 0 0 0
Not Completed 11 84 86 85
Reason Not Completed
Disease Progression             9             61             65             70
Study Discontinued by Sponsor             0             7             5             3
Adverse Event             0             3             6             4
Investigator Discretion             1             4             2             4
Subject Request             1             3             4             2
Subject Withdrew Consent             0             5             2             1
Protocol Violation             0             1             1             0
Death             0             0             0             1
Lost to Follow-up             0             0             1             0
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B) Total
Hide Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months. Total of all reporting groups
Overall Number of Baseline Participants 11 84 86 85 266
Hide Baseline Analysis Population Description
All randomized participants were analyzed.
Age, Customized   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 80 participants 85 participants 84 participants 260 participants
Between 18 and 65 years
7
  63.6%
57
  71.3%
49
  57.6%
56
  66.7%
169
  65.0%
≥ 65 years
4
  36.4%
23
  28.7%
36
  42.4%
28
  33.3%
91
  35.0%
[1]
Measure Description: Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.
[2]
Measure Analysis Population Description: Participants in Full Analysis Set were analyzed.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 80 participants 85 participants 84 participants 260 participants
Female
6
  54.5%
41
  51.2%
32
  37.6%
48
  57.1%
127
  48.8%
Male
5
  45.5%
39
  48.8%
53
  62.4%
36
  42.9%
133
  51.2%
[1]
Measure Analysis Population Description: Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 11 participants 80 participants 85 participants 84 participants 260 participants
White
8
  72.7%
67
  83.8%
74
  87.1%
71
  84.5%
220
  84.6%
Black or African American
2
  18.2%
8
  10.0%
5
   5.9%
7
   8.3%
22
   8.5%
Asian
1
   9.1%
1
   1.3%
5
   5.9%
1
   1.2%
8
   3.1%
Native Hawaiian or Pacific Islander
0
   0.0%
1
   1.3%
0
   0.0%
1
   1.2%
2
   0.8%
Not Permitted
0
   0.0%
3
   3.8%
1
   1.2%
3
   3.6%
7
   2.7%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.2%
1
   0.4%
[1]
Measure Analysis Population Description: Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 11 participants 80 participants 85 participants 84 participants 260 participants
Non-Hispanic/Latino
8
  72.7%
70
  87.5%
75
  88.2%
73
  86.9%
226
  86.9%
Hispanic/Latino
3
  27.3%
5
   6.3%
7
   8.2%
8
   9.5%
23
   8.8%
Not Permitted
0
   0.0%
5
   6.3%
3
   3.5%
3
   3.6%
11
   4.2%
[1]
Measure Analysis Population Description: Participants in Full Analysis Set were analyzed.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
11
 100.0%
45
  53.6%
47
  54.7%
45
  52.9%
148
  55.6%
Poland Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
5
   6.0%
7
   8.1%
5
   5.9%
17
   6.4%
Italy Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
7
   8.3%
7
   8.1%
4
   4.7%
18
   6.8%
France Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
4
   4.8%
1
   1.2%
3
   3.5%
8
   3.0%
Germany Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
5
   6.0%
4
   4.7%
7
   8.2%
16
   6.0%
Spain Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
9
  10.7%
13
  15.1%
8
   9.4%
30
  11.3%
Russia Number Analyzed 11 participants 84 participants 86 participants 85 participants 266 participants
0
   0.0%
9
  10.7%
7
   8.1%
13
  15.3%
29
  10.9%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description The PFS was defined as the time from the date of randomization to the earliest event time of: a) death regardless of cause, or b) first indication of disease progression. PFS was analyzed using Kaplan-Meier (KM) estimates.
Time Frame Randomization up to 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Hide Arm/Group Description:
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months.
Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months.
Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months.
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
Overall Number of Participants Analyzed 11 80 85 84
Median (95% Confidence Interval)
Unit of Measure: months
5.7
(1.8 to 10.0)
5.8
(4.9 to 9.0)
5.4
(3.4 to 5.6)
5.5
(4.0 to 7.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FOLFIRI + Placebo (Part B), FOLFIRI + SIM 200 mg (Part B)
Comments

The null hypothesis was that the hazard ratio (HR) equals to 1 between SIM treatment arm and placebo, while the alternative hypothesis was that HR was less than 1.

The HR (95% confidence interval [CI]) and p-value (for comparison between SIM treatment arm and placebo) were based on two-sided log-rank test, stratified based on the 2-level Eastern Cooperative Oncology Group (ECOG) performance status (0 or > 0) at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0395
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
1.01 to 2.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FOLFIRI + Placebo (Part B), FOLFIRI + SIM 700 mg (Part B)
Comments

The null hypothesis was that the HR equals to 1 between SIM treatment arm and placebo, while the alternative hypothesis was that HR was less than 1.

The HR (95% CI) and p-value (for comparison between SIM treatment arm and placebo) were based on two-sided log-rank test, stratified based on the 2-level ECOG performance status (0 or > 0) at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1042
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.92 to 1.89
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description The OS is measured as time from date of randomization to death regardless of cause. The OS was analyzed using KM estimates.
Time Frame Randomization up to 33 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set were analyzed.
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Hide Arm/Group Description:
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months.
Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months.
Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months.
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
Overall Number of Participants Analyzed 11 80 85 84
Median (95% Confidence Interval)
Unit of Measure: months
9.8
(3.5 to 22.3)
16.3
(12.0 to 19.5)
10.5
(9.2 to 12.6)
11.4
(9.7 to 15.6)
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description Objective response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). The ORR was defined as the percentage of participants who achieved a CR or PR.
Time Frame Randomization up to 27 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set were analyzed.
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Hide Arm/Group Description:
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months.
Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months.
Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months.
Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
Overall Number of Participants Analyzed 11 80 85 84
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.1
(0.2 to 41.3)
10.0
(4.4 to 18.8)
5.9
(1.9 to 13.2)
11.9
(5.9 to 20.8)
Time Frame Randomization up to 33 months
Adverse Event Reporting Description Safety Analysis Set included all participants in the Full Analysis Set grouped for analyses with treatment assignments designated according to the actual study drug received.
 
Arm/Group Title FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Hide Arm/Group Description Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 10 months. Participants received placebo to match SIM via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 27 months. Participants received SIM 200 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 21 months. Participants received SIM 700 mg via intravenous infusion followed by FOLFIRI via intravenous infusion on Days 1 and 15 of each 28-day treatment cycles for approximately 19 months.
All-Cause Mortality
FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/11 (36.36%)   27/80 (33.75%)   24/85 (28.24%)   17/84 (20.24%) 
Blood and lymphatic system disorders         
Anaemia † 1  1/11 (9.09%)  0/80 (0.00%)  1/85 (1.18%)  3/84 (3.57%) 
Febrile neutropenia † 1  0/11 (0.00%)  2/80 (2.50%)  3/85 (3.53%)  1/84 (1.19%) 
Leukopenia † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Neutropenia † 1  0/11 (0.00%)  3/80 (3.75%)  1/85 (1.18%)  2/84 (2.38%) 
Thrombocytopenia † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  1/84 (1.19%) 
Cardiac disorders         
Acute coronary syndrome † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Atrial fibrillation † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Cardiac arrest † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Cardiac failure † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Tachycardia † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Gastrointestinal disorders         
Abdominal pain † 1  1/11 (9.09%)  2/80 (2.50%)  0/85 (0.00%)  1/84 (1.19%) 
Anal fistula † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Diarrhoea † 1  0/11 (0.00%)  1/80 (1.25%)  3/85 (3.53%)  0/84 (0.00%) 
Enteritis † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Intestinal obstruction † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  2/84 (2.38%) 
Intestinal perforation † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Large intestinal obstruction † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Nausea † 1  0/11 (0.00%)  2/80 (2.50%)  0/85 (0.00%)  1/84 (1.19%) 
Small intestinal obstruction † 1  0/11 (0.00%)  1/80 (1.25%)  1/85 (1.18%)  0/84 (0.00%) 
Subileus † 1  0/11 (0.00%)  2/80 (2.50%)  0/85 (0.00%)  0/84 (0.00%) 
Vomiting † 1  0/11 (0.00%)  3/80 (3.75%)  2/85 (2.35%)  1/84 (1.19%) 
General disorders         
Asthenia † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Death † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
General physical health deterioration † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Pyrexia † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  2/84 (2.38%) 
Immune system disorders         
Hypersensitivity † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Infections and infestations         
Bacteraemia † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Device related infection † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  1/84 (1.19%) 
Diverticulitis † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Gastroenteritis † 1  0/11 (0.00%)  2/80 (2.50%)  0/85 (0.00%)  0/84 (0.00%) 
Gastroenteritis viral † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Herpes zoster † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Influenza † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Klebsiella infection † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Lung infection † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Pneumonia † 1  0/11 (0.00%)  2/80 (2.50%)  0/85 (0.00%)  1/84 (1.19%) 
Pyelonephritis † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Respiratory tract infection † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Sepsis † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  3/84 (3.57%) 
Urinary tract infection † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Urosepsis † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  1/84 (1.19%) 
Injury, poisoning and procedural complications         
Ankle fracture † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Hip fracture † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Post procedural haemorrhage † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Radius fracture † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Investigations         
Neutrophil count decreased † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Urine output decreased † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Metabolism and nutrition disorders         
Dehydration † 1  0/11 (0.00%)  2/80 (2.50%)  1/85 (1.18%)  0/84 (0.00%) 
Diabetic ketoacidosis † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Electrolyte imbalance † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Hypoglycaemia † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Hypokalaemia † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Hyponatraemia † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Hypophosphataemia † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Malignant ascites † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Metastases to central nervous system † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Tumour thrombosis † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Nervous system disorders         
Cerebrovascular accident † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Presyncope † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Psychiatric disorders         
Confusional state † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Delirium † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Mental status changes † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Renal and urinary disorders         
Nephrolithiasis † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Renal failure acute † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Renal impairment † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Urinary tract disorder † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Lower respiratory tract inflammation † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Pneumothorax † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Pulmonary embolism † 1  0/11 (0.00%)  4/80 (5.00%)  2/85 (2.35%)  2/84 (2.38%) 
Pulmonary infarction † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Respiratory failure † 1  0/11 (0.00%)  0/80 (0.00%)  0/85 (0.00%)  1/84 (1.19%) 
Vascular disorders         
Deep vein thrombosis † 1  0/11 (0.00%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Superior vena cava occlusion † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Venous thrombosis † 1  0/11 (0.00%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
FOLFIRI + SIM 700 mg (Part A) FOLFIRI + Placebo (Part B) FOLFIRI + SIM 200 mg (Part B) FOLFIRI + SIM 700 mg (Part B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/11 (100.00%)   76/80 (95.00%)   80/85 (94.12%)   79/84 (94.05%) 
Blood and lymphatic system disorders         
Anaemia † 1  3/11 (27.27%)  19/80 (23.75%)  23/85 (27.06%)  18/84 (21.43%) 
Leukopenia † 1  1/11 (9.09%)  9/80 (11.25%)  13/85 (15.29%)  13/84 (15.48%) 
Neutropenia † 1  6/11 (54.55%)  35/80 (43.75%)  42/85 (49.41%)  40/84 (47.62%) 
Thrombocytopenia † 1  0/11 (0.00%)  6/80 (7.50%)  10/85 (11.76%)  11/84 (13.10%) 
Cardiac disorders         
Arrhythmia † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Atrial fibrillation † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Cardiac failure congestive † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Palpitations † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Eye disorders         
Eye pain † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Ocular hyperaemia † 1  1/11 (9.09%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Gastrointestinal disorders         
Abdominal discomfort † 1  1/11 (9.09%)  2/80 (2.50%)  2/85 (2.35%)  0/84 (0.00%) 
Abdominal distension † 1  2/11 (18.18%)  4/80 (5.00%)  2/85 (2.35%)  1/84 (1.19%) 
Abdominal pain † 1  4/11 (36.36%)  18/80 (22.50%)  16/85 (18.82%)  22/84 (26.19%) 
Abdominal pain lower † 1  0/11 (0.00%)  5/80 (6.25%)  0/85 (0.00%)  2/84 (2.38%) 
Abdominal pain upper † 1  2/11 (18.18%)  6/80 (7.50%)  8/85 (9.41%)  6/84 (7.14%) 
Constipation † 1  4/11 (36.36%)  17/80 (21.25%)  18/85 (21.18%)  21/84 (25.00%) 
Diarrhoea † 1  9/11 (81.82%)  43/80 (53.75%)  36/85 (42.35%)  42/84 (50.00%) 
Dry mouth † 1  1/11 (9.09%)  7/80 (8.75%)  2/85 (2.35%)  3/84 (3.57%) 
Dyspepsia † 1  3/11 (27.27%)  7/80 (8.75%)  4/85 (4.71%)  4/84 (4.76%) 
Dysphagia † 1  2/11 (18.18%)  4/80 (5.00%)  0/85 (0.00%)  1/84 (1.19%) 
Gastrooesophageal reflux disease † 1  2/11 (18.18%)  3/80 (3.75%)  3/85 (3.53%)  1/84 (1.19%) 
Haematochezia † 1  1/11 (9.09%)  2/80 (2.50%)  1/85 (1.18%)  0/84 (0.00%) 
Nausea † 1  9/11 (81.82%)  37/80 (46.25%)  38/85 (44.71%)  42/84 (50.00%) 
Oral mucosal erythema † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Oral pain † 1  1/11 (9.09%)  2/80 (2.50%)  3/85 (3.53%)  1/84 (1.19%) 
Salivary hypersecretion † 1  2/11 (18.18%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Stomatitis † 1  1/11 (9.09%)  17/80 (21.25%)  14/85 (16.47%)  9/84 (10.71%) 
Vomiting † 1  5/11 (45.45%)  25/80 (31.25%)  21/85 (24.71%)  23/84 (27.38%) 
General disorders         
Asthenia † 1  2/11 (18.18%)  12/80 (15.00%)  13/85 (15.29%)  12/84 (14.29%) 
Axillary pain † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Catheter site pain † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  1/84 (1.19%) 
Catheter site rash † 1  1/11 (9.09%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Chest discomfort † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  1/84 (1.19%) 
Chest pain † 1  0/11 (0.00%)  3/80 (3.75%)  1/85 (1.18%)  5/84 (5.95%) 
Fatigue † 1  9/11 (81.82%)  34/80 (42.50%)  38/85 (44.71%)  43/84 (51.19%) 
Feeling abnormal † 1  1/11 (9.09%)  0/80 (0.00%)  1/85 (1.18%)  0/84 (0.00%) 
Feeling jittery † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Malaise † 1  1/11 (9.09%)  1/80 (1.25%)  1/85 (1.18%)  5/84 (5.95%) 
Mucosal inflammation † 1  3/11 (27.27%)  10/80 (12.50%)  14/85 (16.47%)  7/84 (8.33%) 
Oedema peripheral † 1  0/11 (0.00%)  4/80 (5.00%)  14/85 (16.47%)  10/84 (11.90%) 
Pyrexia † 1  1/11 (9.09%)  11/80 (13.75%)  10/85 (11.76%)  11/84 (13.10%) 
Infections and infestations         
Infection † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Nasopharyngitis † 1  1/11 (9.09%)  1/80 (1.25%)  2/85 (2.35%)  2/84 (2.38%) 
Pneumonia † 1  1/11 (9.09%)  2/80 (2.50%)  2/85 (2.35%)  0/84 (0.00%) 
Respiratory tract infection † 1  1/11 (9.09%)  1/80 (1.25%)  1/85 (1.18%)  0/84 (0.00%) 
Upper respiratory tract infection † 1  0/11 (0.00%)  5/80 (6.25%)  4/85 (4.71%)  2/84 (2.38%) 
Urinary tract infection † 1  0/11 (0.00%)  6/80 (7.50%)  5/85 (5.88%)  9/84 (10.71%) 
Investigations         
Alanine aminotransferase increased † 1  0/11 (0.00%)  4/80 (5.00%)  4/85 (4.71%)  5/84 (5.95%) 
Aspartate aminotransferase increased † 1  0/11 (0.00%)  5/80 (6.25%)  6/85 (7.06%)  4/84 (4.76%) 
Blood alkaline phosphatase increased † 1  1/11 (9.09%)  6/80 (7.50%)  4/85 (4.71%)  4/84 (4.76%) 
International normalised ratio increased † 1  1/11 (9.09%)  2/80 (2.50%)  2/85 (2.35%)  1/84 (1.19%) 
Neutrophil count decreased † 1  0/11 (0.00%)  5/80 (6.25%)  3/85 (3.53%)  3/84 (3.57%) 
Weight decreased † 1  1/11 (9.09%)  7/80 (8.75%)  9/85 (10.59%)  6/84 (7.14%) 
White blood cell count increased † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite † 1  5/11 (45.45%)  22/80 (27.50%)  14/85 (16.47%)  21/84 (25.00%) 
Dehydration † 1  3/11 (27.27%)  4/80 (5.00%)  5/85 (5.88%)  6/84 (7.14%) 
Hyperglycaemia † 1  1/11 (9.09%)  2/80 (2.50%)  4/85 (4.71%)  3/84 (3.57%) 
Hypoalbuminaemia † 1  1/11 (9.09%)  0/80 (0.00%)  1/85 (1.18%)  1/84 (1.19%) 
Hypocalcaemia † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  2/84 (2.38%) 
Hypokalaemia † 1  0/11 (0.00%)  8/80 (10.00%)  8/85 (9.41%)  10/84 (11.90%) 
Hypomagnesaemia † 1  0/11 (0.00%)  5/80 (6.25%)  2/85 (2.35%)  3/84 (3.57%) 
Hypophosphataemia † 1  1/11 (9.09%)  1/80 (1.25%)  2/85 (2.35%)  2/84 (2.38%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  1/11 (9.09%)  4/80 (5.00%)  4/85 (4.71%)  5/84 (5.95%) 
Back pain † 1  3/11 (27.27%)  6/80 (7.50%)  9/85 (10.59%)  9/84 (10.71%) 
Bone pain † 1  1/11 (9.09%)  2/80 (2.50%)  0/85 (0.00%)  2/84 (2.38%) 
Muscle atrophy † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Muscle spasms † 1  1/11 (9.09%)  5/80 (6.25%)  0/85 (0.00%)  5/84 (5.95%) 
Muscle tightness † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Muscular weakness † 1  2/11 (18.18%)  0/80 (0.00%)  2/85 (2.35%)  0/84 (0.00%) 
Musculoskeletal pain † 1  1/11 (9.09%)  3/80 (3.75%)  1/85 (1.18%)  5/84 (5.95%) 
Pain in extremity † 1  1/11 (9.09%)  3/80 (3.75%)  1/85 (1.18%)  6/84 (7.14%) 
Nervous system disorders         
Dizziness † 1  1/11 (9.09%)  7/80 (8.75%)  9/85 (10.59%)  13/84 (15.48%) 
Dizziness postural † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Dysgeusia † 1  1/11 (9.09%)  6/80 (7.50%)  6/85 (7.06%)  8/84 (9.52%) 
Headache † 1  1/11 (9.09%)  4/80 (5.00%)  3/85 (3.53%)  6/84 (7.14%) 
Neuropathy peripheral † 1  2/11 (18.18%)  5/80 (6.25%)  7/85 (8.24%)  7/84 (8.33%) 
Parosmia † 1  1/11 (9.09%)  1/80 (1.25%)  1/85 (1.18%)  0/84 (0.00%) 
Peripheral sensory neuropathy † 1  1/11 (9.09%)  4/80 (5.00%)  2/85 (2.35%)  3/84 (3.57%) 
VIIth nerve paralysis † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Psychiatric disorders         
Agitation † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Anger † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Anxiety † 1  3/11 (27.27%)  5/80 (6.25%)  5/85 (5.88%)  4/84 (4.76%) 
Depression † 1  1/11 (9.09%)  2/80 (2.50%)  3/85 (3.53%)  3/84 (3.57%) 
Insomnia † 1  5/11 (45.45%)  9/80 (11.25%)  5/85 (5.88%)  8/84 (9.52%) 
Mood swings † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Renal and urinary disorders         
Dysuria † 1  0/11 (0.00%)  5/80 (6.25%)  3/85 (3.53%)  0/84 (0.00%) 
Micturition urgency † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Nocturia † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Cough † 1  1/11 (9.09%)  10/80 (12.50%)  10/85 (11.76%)  14/84 (16.67%) 
Dyspnoea † 1  0/11 (0.00%)  10/80 (12.50%)  9/85 (10.59%)  11/84 (13.10%) 
Dyspnoea exertional † 1  1/11 (9.09%)  0/80 (0.00%)  3/85 (3.53%)  0/84 (0.00%) 
Epistaxis † 1  0/11 (0.00%)  10/80 (12.50%)  5/85 (5.88%)  4/84 (4.76%) 
Hiccups † 1  2/11 (18.18%)  1/80 (1.25%)  1/85 (1.18%)  1/84 (1.19%) 
Oropharyngeal pain † 1  1/11 (9.09%)  3/80 (3.75%)  0/85 (0.00%)  8/84 (9.52%) 
Rhinorrhoea † 1  1/11 (9.09%)  2/80 (2.50%)  2/85 (2.35%)  4/84 (4.76%) 
Throat tightness † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia † 1  6/11 (54.55%)  21/80 (26.25%)  20/85 (23.53%)  22/84 (26.19%) 
Dry skin † 1  0/11 (0.00%)  5/80 (6.25%)  2/85 (2.35%)  5/84 (5.95%) 
Hyperhidrosis † 1  1/11 (9.09%)  3/80 (3.75%)  2/85 (2.35%)  3/84 (3.57%) 
Night sweats † 1  0/11 (0.00%)  4/80 (5.00%)  1/85 (1.18%)  3/84 (3.57%) 
Rash † 1  1/11 (9.09%)  3/80 (3.75%)  4/85 (4.71%)  3/84 (3.57%) 
Skin disorder † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Skin hyperpigmentation † 1  1/11 (9.09%)  1/80 (1.25%)  2/85 (2.35%)  2/84 (2.38%) 
Skin wrinkling † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
Swelling face † 1  1/11 (9.09%)  1/80 (1.25%)  0/85 (0.00%)  0/84 (0.00%) 
Vascular disorders         
Flushing † 1  2/11 (18.18%)  0/80 (0.00%)  2/85 (2.35%)  0/84 (0.00%) 
Hypotension † 1  1/11 (9.09%)  3/80 (3.75%)  2/85 (2.35%)  4/84 (4.76%) 
Peripheral coldness † 1  1/11 (9.09%)  0/80 (0.00%)  0/85 (0.00%)  0/84 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
[Not Specified]
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01479465    
Other Study ID Numbers: GS-US-295-0203
2011-003754-61 ( EudraCT Number )
First Submitted: November 9, 2011
First Posted: November 24, 2011
Results First Submitted: March 26, 2019
Results First Posted: April 17, 2019
Last Update Posted: April 17, 2019