Trial Outcomes & Findings for Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer (NCT NCT01365910)
NCT ID: NCT01365910
Last Updated: 2014-08-26
Results Overview
Per Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Defined as the CR + PR recorded from the start of the treatment until disease progression/recurrence, the exact two-sided 95% confidence intervals will be reported.
TERMINATED
PHASE2
30 participants
Baseline and every 8 weeks, up to 2 years
2014-08-26
Participant Flow
This study opened June 3, 2011 and continued until June 3, 2013. Patients were enrolled at Vanderbilt-Ingram Cancer Center.
Thirty-five patients consented to be on this study. Four patients were considered ineligible, and 1 patient withdrew prior to treatment.
Participant milestones
| Measure |
Treatment (Enzyme Inhibitor)
ABT-869/Linifanib will be administered orally on a daily basis at 17.5 mg/day (fixed dose). The drug is provided in tablets of 2.5 mg or 10 mg tablets.This course of treatment repeats every 28 days until disease progression, intolerability, investigator decision or patient withdrawal of consent.
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
30
|
Reasons for withdrawal
| Measure |
Treatment (Enzyme Inhibitor)
ABT-869/Linifanib will be administered orally on a daily basis at 17.5 mg/day (fixed dose). The drug is provided in tablets of 2.5 mg or 10 mg tablets.This course of treatment repeats every 28 days until disease progression, intolerability, investigator decision or patient withdrawal of consent.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
|
Overall Study
disease progression
|
18
|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
other complicating disease
|
1
|
|
Overall Study
pt did not get tx, nausea/vomiting
|
1
|
Baseline Characteristics
Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Enzyme Inhibitor)
n=30 Participants
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Customized
Age 20-29
|
1 participants
n=5 Participants
|
|
Age, Customized
Age 40-49
|
4 participants
n=5 Participants
|
|
Age, Customized
Age 50-59
|
10 participants
n=5 Participants
|
|
Age, Customized
Age 60-69
|
10 participants
n=5 Participants
|
|
Age, Customized
Age 70-79
|
5 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 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
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and every 8 weeks, up to 2 yearsPopulation: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.
Per Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Defined as the CR + PR recorded from the start of the treatment until disease progression/recurrence, the exact two-sided 95% confidence intervals will be reported.
Outcome measures
| Measure |
Treatment (Enzyme Inhibitor)
n=23 Participants
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%
|
0 percentage of target lesions
Interval 0.0 to 0.148
|
SECONDARY outcome
Timeframe: Every 3 months, up to 2 yearsPopulation: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where either death or progression is an event, with censoring for non-progressed, non-expired patients at greater of off-study date or last known alive date.
Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring. Disease progression is defined under RECIST v1.1 as \>=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.
Outcome measures
| Measure |
Treatment (Enzyme Inhibitor)
n=29 Participants
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Progression-free Survival
|
155 days
Interval 112.0 to 290.0
|
SECONDARY outcome
Timeframe: Every 3 months, up to 2 yearsPopulation: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.
Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring.
Outcome measures
| Measure |
Treatment (Enzyme Inhibitor)
n=29 Participants
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Overall Survival
|
290 days
Interval 158.0 to 367.0
|
SECONDARY outcome
Timeframe: date on-study up to 2 years following final dose of studyPopulation: Total number of patients reported with any toxicity
Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1= mild; grade 2 = moderate; grade 3 = severe; grade 4 = life-threatening; grade 5 = death Assessed: days 1 \&15 of cycle 1; day 1 of each subsequent 28-day cycle; at 30-day follow-up for two years
Outcome measures
| Measure |
Treatment (Enzyme Inhibitor)
n=29 Participants
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Number of Patients With Each Worst-Grade Toxicity
worst grade toxicity 1
|
0 participants
|
|
Number of Patients With Each Worst-Grade Toxicity
worst grade toxicity 2
|
4 participants
|
|
Number of Patients With Each Worst-Grade Toxicity
worst grade toxicity 3
|
23 participants
|
|
Number of Patients With Each Worst-Grade Toxicity
worst grade toxicity 4
|
1 participants
|
|
Number of Patients With Each Worst-Grade Toxicity
worst grade toxicity 5
|
1 participants
|
Adverse Events
Treatment (Enzyme Inhibitor)
Serious adverse events
| Measure |
Treatment (Enzyme Inhibitor)
n=30 participants at risk
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • Number of events 2
|
|
Gastrointestinal disorders
Ascites
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
colonic obstruction
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
constipation
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
diarrhea
|
6.7%
2/30 • Number of events 2
|
|
Gastrointestinal disorders
ileal perforation
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
6.7%
2/30 • Number of events 4
|
|
Gastrointestinal disorders
gastric obstruction
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
small intestine obstruction
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
3.3%
1/30 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
2/30 • Number of events 3
|
|
General disorders
General disorders and administration site conditions Pain
|
10.0%
3/30 • Number of events 3
|
|
Hepatobiliary disorders
Bile duct stenosis
|
3.3%
1/30 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic failure
|
3.3%
1/30 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
10.0%
3/30 • Number of events 3
|
|
Metabolism and nutrition disorders
dehydration
|
10.0%
3/30 • Number of events 3
|
|
Psychiatric disorders
confusion
|
3.3%
1/30 • Number of events 1
|
|
Renal and urinary disorders
acute kidney injury
|
3.3%
1/30 • Number of events 1
|
|
Vascular disorders
Thromboembolic event
|
3.3%
1/30 • Number of events 1
|
Other adverse events
| Measure |
Treatment (Enzyme Inhibitor)
n=30 participants at risk
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
linifanib: Given PO
|
|---|---|
|
Gastrointestinal disorders
diarrhea
|
56.7%
17/30 • Number of events 29
|
|
Gastrointestinal disorders
abdominal pain
|
50.0%
15/30 • Number of events 27
|
|
Gastrointestinal disorders
nausea
|
50.0%
15/30 • Number of events 26
|
|
Gastrointestinal disorders
oral pain
|
33.3%
10/30 • Number of events 24
|
|
Gastrointestinal disorders
vomiting
|
33.3%
10/30 • Number of events 16
|
|
Gastrointestinal disorders
mucositis oral
|
23.3%
7/30 • Number of events 10
|
|
Gastrointestinal disorders
constipation
|
20.0%
6/30 • Number of events 9
|
|
Gastrointestinal disorders
dyspepsia
|
16.7%
5/30 • Number of events 5
|
|
Gastrointestinal disorders
hemorrhoids
|
13.3%
4/30 • Number of events 4
|
|
Gastrointestinal disorders
gastrointestinal disorders, other
|
10.0%
3/30 • Number of events 3
|
|
Gastrointestinal disorders
gingival pain
|
6.7%
2/30 • Number of events 2
|
|
General disorders
fatigue
|
80.0%
24/30 • Number of events 78
|
|
General disorders
pain
|
26.7%
8/30 • Number of events 12
|
|
General disorders
edema
|
13.3%
4/30 • Number of events 5
|
|
General disorders
chills
|
6.7%
2/30 • Number of events 2
|
|
General disorders
fever
|
6.7%
2/30 • Number of events 2
|
|
Investigations
alkaline phosphatase increased
|
50.0%
15/30 • Number of events 26
|
|
Investigations
aspartate aminotransferase increased
|
50.0%
15/30 • Number of events 30
|
|
Investigations
activated partial thromboplastin time increase
|
40.0%
12/30 • Number of events 19
|
|
Gastrointestinal disorders
rectal hemorrhage
|
6.7%
2/30 • Number of events 2
|
|
Investigations
weight loss
|
36.7%
11/30 • Number of events 17
|
|
Investigations
alanine aminotransferase
|
30.0%
9/30 • Number of events 15
|
|
Investigations
platelet count decreased
|
26.7%
8/30 • Number of events 16
|
|
Investigations
white blood cell decreased
|
23.3%
7/30 • Number of events 14
|
|
Investigations
lymphocyte count decreased
|
20.0%
6/30 • Number of events 17
|
|
Investigations
blood bilirubin increased
|
13.3%
4/30 • Number of events 9
|
|
Investigations
neutrophil count decreased
|
6.7%
2/30 • Number of events 2
|
|
Metabolism and nutrition disorders
anexoria
|
46.7%
14/30 • Number of events 20
|
|
Metabolism and nutrition disorders
hyponatremia
|
46.7%
14/30 • Number of events 33
|
|
Metabolism and nutrition disorders
hypoalbuminemia
|
43.3%
13/30 • Number of events 20
|
|
Metabolism and nutrition disorders
hyperglycemia
|
23.3%
7/30 • Number of events 11
|
|
Metabolism and nutrition disorders
hypokalemia
|
23.3%
7/30 • Number of events 11
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
23.3%
7/30 • Number of events 9
|
|
Metabolism and nutrition disorders
hypercalcemia
|
10.0%
3/30 • Number of events 3
|
|
Metabolism and nutrition disorders
dehydration
|
6.7%
2/30 • Number of events 2
|
|
Metabolism and nutrition disorders
hypocalcemia
|
6.7%
2/30 • Number of events 3
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
6.7%
2/30 • Number of events 2
|
|
Renal and urinary disorders
proteinuria
|
60.0%
18/30 • Number of events 44
|
|
Renal and urinary disorders
hematuria
|
33.3%
10/30 • Number of events 13
|
|
Renal and urinary disorders
urinary tract obstruction
|
6.7%
2/30 • Number of events 2
|
|
Vascular disorders
hypertension
|
66.7%
20/30 • Number of events 109
|
|
Vascular disorders
hypotension
|
10.0%
3/30 • Number of events 3
|
|
Blood and lymphatic system disorders
anemia
|
66.7%
20/30 • Number of events 39
|
|
Respiratory, thoracic and mediastinal disorders
hoarseness
|
40.0%
12/30 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
20.0%
6/30 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
10.0%
3/30 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
laryngeal inflammation
|
10.0%
3/30 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
sore throat
|
6.7%
2/30 • Number of events 3
|
|
Endocrine disorders
endrocrine disorders, other
|
26.7%
8/30 • Number of events 13
|
|
Endocrine disorders
hypothyroidism
|
26.7%
8/30 • Number of events 11
|
|
Nervous system disorders
headache
|
23.3%
7/30 • Number of events 10
|
|
Nervous system disorders
dysgeusia
|
20.0%
6/30 • Number of events 8
|
|
Nervous system disorders
dizziness
|
10.0%
3/30 • Number of events 3
|
|
Nervous system disorders
somnolence
|
10.0%
3/30 • Number of events 4
|
|
Nervous system disorders
tremor
|
10.0%
3/30 • Number of events 3
|
|
Nervous system disorders
dysarthria
|
6.7%
2/30 • Number of events 2
|
|
Nervous system disorders
peripheral sensory neuropathy
|
6.7%
2/30 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
palmar-olantar erthrodysesthesia syndrome
|
30.0%
9/30 • Number of events 63
|
|
Skin and subcutaneous tissue disorders
skin and subcutaneous tissue disorders, other
|
20.0%
6/30 • Number of events 15
|
|
Skin and subcutaneous tissue disorders
dry skin
|
16.7%
5/30 • Number of events 5
|
|
Infections and infestations
upper respiratory infection
|
10.0%
3/30 • Number of events 3
|
|
Infections and infestations
urinary tract infection
|
10.0%
3/30 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
20.0%
6/30 • Number of events 14
|
|
Musculoskeletal and connective tissue disorders
back pain
|
10.0%
3/30 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
10.0%
3/30 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
extremity pain
|
6.7%
2/30 • Number of events 2
|
|
Psychiatric disorders
anxiety
|
13.3%
4/30 • Number of events 4
|
|
Psychiatric disorders
depression
|
10.0%
3/30 • Number of events 4
|
|
Psychiatric disorders
confusion
|
6.7%
2/30 • Number of events 2
|
|
Cardiac disorders
sinus tachycardia
|
13.3%
4/30 • Number of events 4
|
|
Injury, poisoning and procedural complications
bruising
|
10.0%
3/30 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place