Trial Outcomes & Findings for Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib. (NCT NCT01289028)
NCT ID: NCT01289028
Last Updated: 2017-01-02
Results Overview
Neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progression Disease, taking as reference the smallest sum of the longest diameter since the treatment started.
COMPLETED
PHASE3
125 participants
During the first 4 months
2017-01-02
Participant Flow
Participant milestones
| Measure |
Nilotinib
|
|---|---|
|
Overall Study
STARTED
|
125
|
|
Overall Study
COMPLETED
|
42
|
|
Overall Study
NOT COMPLETED
|
83
|
Reasons for withdrawal
| Measure |
Nilotinib
|
|---|---|
|
Overall Study
Progressive Disease
|
49
|
|
Overall Study
Adverse Event
|
14
|
|
Overall Study
Withdrawal by Subject
|
6
|
|
Overall Study
Death
|
4
|
|
Overall Study
Lack of Efficacy
|
2
|
|
Overall Study
No longer required
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
New Cancer Therapy
|
2
|
|
Overall Study
Abnormal Lab Value
|
1
|
|
Overall Study
Missing reason for discon
|
1
|
Baseline Characteristics
Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.
Baseline characteristics by cohort
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Age, Continuous
|
60 years
STANDARD_DEVIATION 12.1 • n=5 Participants
|
|
Gender
Female
|
46 Participants
n=5 Participants
|
|
Gender
Male
|
79 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During the first 4 monthsNeither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progression Disease, taking as reference the smallest sum of the longest diameter since the treatment started.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Percent of Patients Achieving Stable Disease (SD)
|
48.8 % participants
|
PRIMARY outcome
Timeframe: during the first 4 monthsPopulation: ITT set, N=125
The primary efficacy variable was defined as the proportion of patients with a best overall response of CR by Week 16/Month 4 based on local assessment according to RECIST (Version 1.0). This is an at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Percent of Patients Achieving Partial Response (PR)
|
0 percentage of participants
|
PRIMARY outcome
Timeframe: during the first 4 monthsComplete response (CR) is the Disappearance of all target lesions.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Percent of Patients Achieving Complete Response (CR)
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 24 weeks and 52 weeksPopulation: ITT population
Complete Response (CR): Disappearance of all target lesions. and Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population
24 weeks
|
92.0 percentage of participants
|
|
Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population
52 weeks
|
92.0 percentage of participants
|
SECONDARY outcome
Timeframe: 24 weeks and 52 weeksComplete Response (CR): Disappearance of all target lesions, and Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
Outcome measures
| Measure |
Nilotinib
n=98 Participants
|
|---|---|
|
Time to Overall Response (CR or PR): Per Protocol Population
24 weeks
|
91.2 percentage of participants
|
|
Time to Overall Response (CR or PR): Per Protocol Population
52 weeks
|
91.2 percentage of participants
|
SECONDARY outcome
Timeframe: during the first 4 monthsPopulation: Time to tumor progression defined as the time from start of treatment to observed tumor progression (censoring for death without progression) as stated in the original protocol was not evaluated
Time to tumor progression defined as the time from start of treatment to observed tumor progression (censoring for death without progression) as stated in the original protocol was not evaluated as stated in section 9.8.3 of the clinical study report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: during 12 monthsThe best overall response is the best response recorded from the start of the treatment until disease progression/recurrence
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Duration of Overall Response
|
1331 days
Interval 366.0 to
Due to number of censored cases (insufficient number of participants with measurable events) Upper Limit CI was not possible to calculate.
|
SECONDARY outcome
Timeframe: during 12 monthsThe OS rate could not be calculated due to the high number of censored cases. Number of censored, n (%) 108 (86.4). Only available data is number of events. OS was defined as the time from first study drug administration to death from any cause. If a patient was not known to have died, survival was censored at date of last contact.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Overall Survival, Number of Events Related to Progression of the Disease
|
17 events
|
SECONDARY outcome
Timeframe: during 12 monthsProgression-free survival (PFS) is defined as the time from first study drug administration to objective tumor progression or death from any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
Outcome measures
| Measure |
Nilotinib
n=125 Participants
|
|---|---|
|
Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment.
|
110 days
Interval 64.0 to 118.0
|
Adverse Events
All Patients
Serious adverse events
| Measure |
All Patients
n=125 participants at risk
All patients
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.80%
1/125
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.80%
1/125
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.80%
1/125
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
2.4%
3/125
|
|
Nervous system disorders
Intercostal neuralgia
|
0.80%
1/125
|
|
Renal and urinary disorders
Hydronephrosis
|
0.80%
1/125
|
|
Renal and urinary disorders
Renal failure
|
1.6%
2/125
|
|
Renal and urinary disorders
Renal failure acute
|
0.80%
1/125
|
|
Renal and urinary disorders
Ureteric stenosis
|
0.80%
1/125
|
|
Renal and urinary disorders
Urethral stenosis
|
0.80%
1/125
|
|
Renal and urinary disorders
Urinary retention
|
0.80%
1/125
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.80%
1/125
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.80%
1/125
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.80%
1/125
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.80%
1/125
|
|
Vascular disorders
Arterial occlusive disease
|
0.80%
1/125
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.80%
1/125
|
|
Blood and lymphatic system disorders
Anaemia
|
4.8%
6/125
|
|
Cardiac disorders
Acute coronary syndrome
|
0.80%
1/125
|
|
Cardiac disorders
Angina unstable
|
0.80%
1/125
|
|
Cardiac disorders
Aortic valve stenosis
|
0.80%
1/125
|
|
Cardiac disorders
Atrial fibrillation
|
0.80%
1/125
|
|
Cardiac disorders
Cardiac failure
|
0.80%
1/125
|
|
Cardiac disorders
Coronary artery stenosis
|
0.80%
1/125
|
|
Cardiac disorders
Myocardial infarction
|
1.6%
2/125
|
|
Gastrointestinal disorders
Abdominal pain
|
5.6%
7/125
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.80%
1/125
|
|
Gastrointestinal disorders
Abdominal wall mass
|
0.80%
1/125
|
|
Gastrointestinal disorders
Ascites
|
1.6%
2/125
|
|
Gastrointestinal disorders
Constipation
|
2.4%
3/125
|
|
Gastrointestinal disorders
Diarrhoea
|
0.80%
1/125
|
|
Gastrointestinal disorders
Flatulence
|
0.80%
1/125
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.80%
1/125
|
|
Gastrointestinal disorders
Melaena
|
0.80%
1/125
|
|
Gastrointestinal disorders
Mesenteric haemorrhage
|
0.80%
1/125
|
|
Gastrointestinal disorders
Nausea
|
1.6%
2/125
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.80%
1/125
|
|
Gastrointestinal disorders
Subileus
|
0.80%
1/125
|
|
Gastrointestinal disorders
Vomiting
|
4.0%
5/125
|
|
General disorders
Asthenia
|
0.80%
1/125
|
|
General disorders
Chest pain
|
0.80%
1/125
|
|
General disorders
Chills
|
0.80%
1/125
|
|
General disorders
Condition aggravated
|
1.6%
2/125
|
|
General disorders
Device occlusion
|
1.6%
2/125
|
|
General disorders
Disease progression
|
4.8%
6/125
|
|
General disorders
Fatigue
|
2.4%
3/125
|
|
General disorders
General physical health deterioration
|
2.4%
3/125
|
|
General disorders
Multi-organ failure
|
0.80%
1/125
|
|
General disorders
Obstruction
|
0.80%
1/125
|
|
General disorders
Pyrexia
|
4.0%
5/125
|
|
Hepatobiliary disorders
Cholangitis
|
0.80%
1/125
|
|
Hepatobiliary disorders
Cholestasis
|
0.80%
1/125
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.80%
1/125
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.80%
1/125
|
|
Infections and infestations
Breast abscess
|
0.80%
1/125
|
|
Infections and infestations
Infected skin ulcer
|
0.80%
1/125
|
|
Infections and infestations
Infection
|
0.80%
1/125
|
|
Infections and infestations
Pneumonia
|
0.80%
1/125
|
|
Infections and infestations
Rectal abscess
|
0.80%
1/125
|
|
Infections and infestations
Sinusitis
|
0.80%
1/125
|
|
Infections and infestations
Staphylococcal infection
|
0.80%
1/125
|
|
Infections and infestations
Urinary tract infection
|
0.80%
1/125
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.80%
1/125
|
|
Injury, poisoning and procedural complications
Concussion
|
0.80%
1/125
|
|
Injury, poisoning and procedural complications
Lip injury
|
0.80%
1/125
|
|
Investigations
Amylase increased
|
0.80%
1/125
|
|
Investigations
Blood creatinine increased
|
1.6%
2/125
|
|
Investigations
C-reactive protein increased
|
1.6%
2/125
|
|
Investigations
Electrocardiogram QT prolonged
|
0.80%
1/125
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.80%
1/125
|
|
Investigations
Haemoglobin decreased
|
0.80%
1/125
|
|
Investigations
Lipase increased
|
1.6%
2/125
|
|
Investigations
Weight decreased
|
1.6%
2/125
|
|
Metabolism and nutrition disorders
Cachexia
|
0.80%
1/125
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.80%
1/125
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.80%
1/125
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.80%
1/125
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.80%
1/125
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
2.4%
3/125
|
Other adverse events
| Measure |
All Patients
n=125 participants at risk
All patients
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.2%
14/125
|
|
Gastrointestinal disorders
Abdominal pain
|
22.4%
28/125
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.6%
7/125
|
|
Gastrointestinal disorders
Constipation
|
25.6%
32/125
|
|
Gastrointestinal disorders
Diarrhoea
|
14.4%
18/125
|
|
Gastrointestinal disorders
Flatulence
|
10.4%
13/125
|
|
Gastrointestinal disorders
Nausea
|
22.4%
28/125
|
|
Gastrointestinal disorders
Vomiting
|
16.8%
21/125
|
|
General disorders
Asthenia
|
8.0%
10/125
|
|
General disorders
Fatigue
|
35.2%
44/125
|
|
General disorders
Oedema peripheral
|
13.6%
17/125
|
|
General disorders
Pyrexia
|
15.2%
19/125
|
|
Infections and infestations
Nasopharyngitis
|
9.6%
12/125
|
|
Investigations
Alanine aminotransferase increased
|
6.4%
8/125
|
|
Investigations
Blood alkaline phosphatase increased
|
12.8%
16/125
|
|
Investigations
C-reactive protein increased
|
7.2%
9/125
|
|
Investigations
Lipase increased
|
5.6%
7/125
|
|
Investigations
Transaminases increased
|
5.6%
7/125
|
|
Investigations
Weight decreased
|
11.2%
14/125
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.4%
18/125
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.6%
7/125
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.4%
8/125
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.8%
11/125
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.2%
9/125
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.0%
10/125
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.8%
11/125
|
|
Nervous system disorders
Headache
|
11.2%
14/125
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.4%
8/125
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.4%
8/125
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.0%
10/125
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.0%
10/125
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.8%
21/125
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.0%
10/125
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER