Trial Outcomes & Findings for Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib (NCT NCT01831726)
NCT ID: NCT01831726
Last Updated: 2017-03-20
Results Overview
CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1
COMPLETED
PHASE2
80 participants
Week 16
2017-03-20
Participant Flow
Participant milestones
| Measure |
TKI258
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Overall Study
STARTED
|
80
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
80
|
Reasons for withdrawal
| Measure |
TKI258
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Overall Study
Adverse Event
|
16
|
|
Overall Study
Death
|
7
|
|
Overall Study
Disease Progression
|
49
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Subject/guardian decision
|
7
|
Baseline Characteristics
Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib
Baseline characteristics by cohort
| Measure |
TKI258
n=80 Participants
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 11.62 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 16Population: Full Analysis Set (FAS) included all patients who received at least one dose of study drug. FAS was used for the analysis of efficacy endpoints.
CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1
Outcome measures
| Measure |
TKI258
n=80 Participants
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Clinical Benefit Rate (CBR)
Complete response (CR)
|
0 number of participants
|
|
Clinical Benefit Rate (CBR)
Partial response (PR)
|
1 number of participants
|
|
Clinical Benefit Rate (CBR)
Stable disease (SD)
|
10 number of participants
|
|
Clinical Benefit Rate (CBR)
Clinical benefit rate (CBR)
|
11 number of participants
|
SECONDARY outcome
Timeframe: Week 16Population: Full Analysis Set (FAS) included all patients who received at least one dose of study drug. FAS was used for the analysis of efficacy endpoints.
Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply and are included in the appendices. ORR: CR+PR
Outcome measures
| Measure |
TKI258
n=80 Participants
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Overall Response (OR) of Partial Response (PR) or Greater
Complete response (CR)
|
0 number of participants
|
|
Overall Response (OR) of Partial Response (PR) or Greater
Partial response (PR)
|
1 number of participants
|
|
Overall Response (OR) of Partial Response (PR) or Greater
Overall response rate (ORR)
|
1 number of participants
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: Full Analysis Set (FAS) included all patients who received at least one dose of study drug. FAS was used for the analysis of efficacy endpoints.
Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.
Outcome measures
| Measure |
TKI258
n=80 Participants
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Progression-Free Survival (PFS)
|
2.4 months
Interval 1.8 to 3.7
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: Full Analysis Set (FAS) included all patients who received at least one dose of study drug. FAS was used for the analysis of efficacy endpoints.
Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact
Outcome measures
| Measure |
TKI258
n=80 Participants
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Overall Survival (OS)
|
13.5 months
Interval 5.9 to 14.7
|
Adverse Events
TKI258
Serious adverse events
| Measure |
TKI258
n=80 participants at risk
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.2%
1/80
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.5%
2/80
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.2%
1/80
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.5%
2/80
|
|
Cardiac disorders
Cardiac arrest
|
1.2%
1/80
|
|
Gastrointestinal disorders
Abdominal pain
|
2.5%
2/80
|
|
Gastrointestinal disorders
Diarrhoea
|
1.2%
1/80
|
|
Gastrointestinal disorders
Dysphagia
|
1.2%
1/80
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.2%
1/80
|
|
Gastrointestinal disorders
Nausea
|
2.5%
2/80
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.2%
1/80
|
|
Gastrointestinal disorders
Stomatitis
|
1.2%
1/80
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
5/80
|
|
General disorders
Chest pain
|
2.5%
2/80
|
|
General disorders
Fatigue
|
1.2%
1/80
|
|
General disorders
Pyrexia
|
2.5%
2/80
|
|
Hepatobiliary disorders
Bile duct obstruction
|
1.2%
1/80
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
1.2%
1/80
|
|
Infections and infestations
Cellulitis
|
1.2%
1/80
|
|
Infections and infestations
Peritonitis
|
1.2%
1/80
|
|
Infections and infestations
Pneumonia
|
1.2%
1/80
|
|
Infections and infestations
Urinary tract infection
|
1.2%
1/80
|
|
Infections and infestations
Wound infection
|
1.2%
1/80
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
1.2%
1/80
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.2%
1/80
|
|
Investigations
Blood alkaline phosphatase increased
|
1.2%
1/80
|
|
Investigations
Blood bilirubin increased
|
2.5%
2/80
|
|
Investigations
Platelet count decreased
|
1.2%
1/80
|
|
Metabolism and nutrition disorders
Dehydration
|
5.0%
4/80
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.2%
1/80
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
1/80
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.2%
1/80
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
1.2%
1/80
|
|
Nervous system disorders
Cerebral thrombosis
|
1.2%
1/80
|
|
Nervous system disorders
Encephalopathy
|
1.2%
1/80
|
|
Nervous system disorders
Lethargy
|
1.2%
1/80
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.2%
1/80
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.2%
1/80
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.5%
2/80
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.2%
1/80
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.2%
1/80
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.0%
4/80
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
1.2%
1/80
|
|
Vascular disorders
Deep vein thrombosis
|
1.2%
1/80
|
|
Vascular disorders
Hypertension
|
1.2%
1/80
|
Other adverse events
| Measure |
TKI258
n=80 participants at risk
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.0%
8/80
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.0%
4/80
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
8/80
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
4/80
|
|
Eye disorders
Lacrimation increased
|
6.2%
5/80
|
|
Gastrointestinal disorders
Abdominal pain
|
15.0%
12/80
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.0%
4/80
|
|
Gastrointestinal disorders
Constipation
|
32.5%
26/80
|
|
Gastrointestinal disorders
Diarrhoea
|
63.7%
51/80
|
|
Gastrointestinal disorders
Dry mouth
|
7.5%
6/80
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
8/80
|
|
Gastrointestinal disorders
Dysphagia
|
5.0%
4/80
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.0%
4/80
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.0%
4/80
|
|
Gastrointestinal disorders
Nausea
|
58.8%
47/80
|
|
Gastrointestinal disorders
Vomiting
|
43.8%
35/80
|
|
General disorders
Asthenia
|
16.2%
13/80
|
|
General disorders
Fatigue
|
70.0%
56/80
|
|
General disorders
Mucosal inflammation
|
5.0%
4/80
|
|
General disorders
Oedema peripheral
|
6.2%
5/80
|
|
General disorders
Pain
|
8.8%
7/80
|
|
General disorders
Pyrexia
|
8.8%
7/80
|
|
Infections and infestations
Pneumonia
|
5.0%
4/80
|
|
Infections and infestations
Upper respiratory tract infection
|
8.8%
7/80
|
|
Infections and infestations
Urinary tract infection
|
8.8%
7/80
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
16/80
|
|
Investigations
Amylase increased
|
10.0%
8/80
|
|
Investigations
Aspartate aminotransferase increased
|
23.8%
19/80
|
|
Investigations
Blood alkaline phosphatase increased
|
28.7%
23/80
|
|
Investigations
Blood bilirubin increased
|
8.8%
7/80
|
|
Investigations
Blood creatinine increased
|
5.0%
4/80
|
|
Investigations
Gamma-glutamyltransferase increased
|
21.2%
17/80
|
|
Investigations
Lipase increased
|
10.0%
8/80
|
|
Investigations
Platelet count decreased
|
5.0%
4/80
|
|
Investigations
Weight decreased
|
22.5%
18/80
|
|
Investigations
White blood cell count decreased
|
7.5%
6/80
|
|
Metabolism and nutrition disorders
Decreased appetite
|
42.5%
34/80
|
|
Metabolism and nutrition disorders
Dehydration
|
21.2%
17/80
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
6.2%
5/80
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.5%
6/80
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.0%
4/80
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
33.8%
27/80
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
10.0%
8/80
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.2%
5/80
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.0%
4/80
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
11.2%
9/80
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
15.0%
12/80
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.0%
4/80
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.5%
6/80
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.0%
12/80
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.5%
6/80
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.2%
5/80
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.5%
6/80
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.2%
9/80
|
|
Nervous system disorders
Dizziness
|
12.5%
10/80
|
|
Nervous system disorders
Dysgeusia
|
11.2%
9/80
|
|
Nervous system disorders
Headache
|
18.8%
15/80
|
|
Nervous system disorders
Neuropathy peripheral
|
6.2%
5/80
|
|
Psychiatric disorders
Anxiety
|
5.0%
4/80
|
|
Psychiatric disorders
Insomnia
|
5.0%
4/80
|
|
Renal and urinary disorders
Proteinuria
|
5.0%
4/80
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.5%
14/80
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
23.8%
19/80
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
5.0%
4/80
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.2%
5/80
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.0%
4/80
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
7.5%
6/80
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
8/80
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.8%
11/80
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.5%
6/80
|
|
Vascular disorders
Hypertension
|
17.5%
14/80
|
|
Vascular disorders
Hypotension
|
10.0%
8/80
|
Additional Information
Study Director
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER