Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01478373
• Collaborator: (none)
• Enrollment: 39
• Locations: 15
• Arm: 1
• Duration (Months): 30
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Dovitinib in patients with gastrointestinal stromal tumors refractory and/or intolerant to Imatinib

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: Dovitinib (TKI258)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: DOVIGIST: Phase II Trial to Evaluate the Efficacy and Safety of Dovitinib (TKI258) in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dovitinib (TKI258) Patients will receive Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.	Drug: Dovitinib (TKI258); Oral Dovitinib (TKI258) as a gelatin capsule of 100 mg strength and dosed on a flat scale of 500 mg on a 5 days on /2 days off dosing schedule.

Outcome Measures

Primary Outcome Measures

1. Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease [12 Weeks]

   DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Secondary Outcome Measures

1. Progression-free Survival (PFS) of Patients Treated With Dovitinib [9 months]

   The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

2. Time to Treatment Failure (TTF)of Patients Treated With Dovitinib [9 months]

   TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.

3. Duration of Response or Stable Disease (SD) [9 months]

   Duration of response or SD: time from date of entry into study to earliest date of first objective tumor progression or death. DCR is defined as proportion of patients with best overall response of CR, PR and SD at 12 weeks according to RECIST (version 1.1). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1; PR: At least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

4. Time to Tumor Progression (TTP)of Patients Treated With Dovitinib [9 months]

   TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

5. Overall Response Rate (ORR) of Patients Treated With Dovitinib [Baseline, 12 weeks]

   Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

6. Overall Survival (OS) of Patients Treated With Dovitinib [21 months (9 months of estimated treatment plus 12 months of survival follow up)]

   Outcome Measure Description: OS: time from the date of entry into the study to the date of death due to any cause. A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.

7. DCR (CR+PR+SD) at the End of Treatment [Up to 9 months of estimated treatment]

   DCR is defined as the proportion of patients with a best overall response of CR, PR and SD at the end of dovitinib treatment according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed GIST of any anatomical location, which is 1) unresectable and/ or metastatic with documented disease progression while on therapy with imatinib or 2) surgically removed localized GIST, recurrent on adjuvant imatinib or recurrent within the first 3 months after discontinuation of adjuvant imatinib or 3) patients with unresectable and/or metastatic GIST intolerant to imatinib

• Positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA gene

• Documented disease progression according to RECIST (version 1.1) on prior therapy with imatinib at a dose of at least 400mg/day or patients with unresectable and/or metastatic GIST who are intolerant to imatinib

• At least one measurable GIST lesion according to RECIST (version 1.1).

• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST

• Patients who received cytotoxic drugs ≤ 4 weeks prior to starting Dovitinib (TKI258)

• Patients who are treated or planned to be treated concomitantly with other cytotoxic or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy

• Patients with another primary malignancy within 3 years prior to starting the study drug

• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting Dovitinib (TKI258) or who have not recovered from the adverse effects of such therapy

• Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months

• Patients with impaired cardiac function or clinically significant cardiac diseases

• Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dovitinib

• Patients with prior complete gastrectomy

• Patients with brain metastasis or history of brain metastasis

• Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or equivalent anticoagulant

• Pregnant or breast-feeding women

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	HUS		Finland	FIN-00029
2	Novartis Investigative Site	Bordeaux		France	33076
3	Novartis Investigative Site	Lille Cedex		France	59020
4	Novartis Investigative Site	Lyon Cedex		France	69373
5	Novartis Investigative Site	Reims		France	51092
6	Novartis Investigative Site	Villejuif Cedex		France	94805
7	Novartis Investigative Site	Essen		Germany	45147
8	Novartis Investigative Site	Milano	MI	Italy	20133
9	Novartis Investigative Site	Roma	RM	Italy	00168
10	Novartis Investigative Site	Candiolo	TO	Italy	10060
11	Novartis Investigative Site	Torino	TO	Italy	10153
12	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
13	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
14	Novartis Investigative Site	Palma De Mallorca	Islas Baleares	Spain	07120
15	Novartis Investigative Site	Barcelona		Spain	08041

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Director: Study Director, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01478373
• Other Study ID Numbers: CTKI258AIC02; 2011-001725-24
• First Posted: Nov 23, 2011
• Last Update Posted: Apr 27, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Novartis Pharmaceuticals: GIST; Dovitinib
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors

Study Results

Participant Flow

Pre-assignment Detail	39 Patients enrolled. One patient had a protocol deviation which excluded him from the Full Analysis Set.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Period Title: Treatment Phase
STARTED	39
COMPLETED	38
NOT COMPLETED	1
Period Title: Treatment Phase
STARTED	38
COMPLETED	0
NOT COMPLETED	38

Baseline Characteristics

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Participants	38
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.2 (10.14)
Sex: Female, Male (Count of Participants)
Female	16 42.1%
Male	22 57.9%

Outcome Measures

1. Primary Outcome

Title	Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
Description	DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Number (90% Confidence Interval) [Percentage of Participants]	52.6 138.4%

2. Secondary Outcome

Title	Progression-free Survival (PFS) of Patients Treated With Dovitinib
Description	The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Median (90% Confidence Interval) [Days]	141

3. Secondary Outcome

Title	Time to Treatment Failure (TTF)of Patients Treated With Dovitinib
Description	TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Median (95% Confidence Interval) [Days]	122.0

4. Secondary Outcome

Title	Duration of Response or Stable Disease (SD)
Description	Duration of response or SD: time from date of entry into study to earliest date of first objective tumor progression or death. DCR is defined as proportion of patients with best overall response of CR, PR and SD at 12 weeks according to RECIST (version 1.1). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1; PR: At least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Mean (Standard Deviation) [Days]	193.2 (117.78)

5. Secondary Outcome

Title	Time to Tumor Progression (TTP)of Patients Treated With Dovitinib
Description	TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Median (95% Confidence Interval) [Days]	141.0

6. Secondary Outcome

Title	Overall Response Rate (ORR) of Patients Treated With Dovitinib
Description	Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Number (90% Confidence Interval) [Percentage of Participants]	2.6 6.8%

7. Secondary Outcome

Title	Overall Survival (OS) of Patients Treated With Dovitinib
Description	Outcome Measure Description: OS: time from the date of entry into the study to the date of death due to any cause. A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.
Time Frame	21 months (9 months of estimated treatment plus 12 months of survival follow up)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Median (95% Confidence Interval) [Months]	NA

8. Secondary Outcome

Title	DCR (CR+PR+SD) at the End of Treatment
Description	DCR is defined as the proportion of patients with a best overall response of CR, PR and SD at the end of dovitinib treatment according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
Time Frame	Up to 9 months of estimated treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
Measure Participants	38
Number (90% Confidence Interval) [Percentage of Participants]	52.6 138.4%

Adverse Events

Arm/Group Title	Dovitinib
Arm/Group Description	Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
All Cause Mortality
	Dovitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dovitinib
	Affected / at Risk (%)	# Events
Total	16/39 (41%)
Blood and lymphatic system disorders
Anaemia	1/39 (2.6%)
Leukopenia	1/39 (2.6%)
Pancytopenia	1/39 (2.6%)
Cardiac disorders
Cardiac arrest	1/39 (2.6%)
Tachycardia	1/39 (2.6%)
Gastrointestinal disorders
Abdominal pain	1/39 (2.6%)
Abdominal pain upper	1/39 (2.6%)
Ascites	1/39 (2.6%)
Diarrhoea	2/39 (5.1%)
Nausea	1/39 (2.6%)
Peritoneal haemorrhage	1/39 (2.6%)
Vomiting	3/39 (7.7%)
General disorders
Asthenia	1/39 (2.6%)
Fatigue	4/39 (10.3%)
General physical health deterioration	1/39 (2.6%)
Inflammation	1/39 (2.6%)
Localised oedema	1/39 (2.6%)
Mucosal dryness	1/39 (2.6%)
Oedema peripheral	1/39 (2.6%)
Systemic inflammatory response syndrome	1/39 (2.6%)
Hepatobiliary disorders
Cholestasis	1/39 (2.6%)
Infections and infestations
H1N1 influenza	1/39 (2.6%)
Tracheobronchitis	1/39 (2.6%)
Investigations
Red blood cell count decreased	1/39 (2.6%)
Weight decreased	1/39 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	2/39 (5.1%)
Dehydration	1/39 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/39 (2.6%)
Prostate cancer	1/39 (2.6%)
Nervous system disorders
Neuropathy peripheral	1/39 (2.6%)
Paraesthesia	1/39 (2.6%)
Psychiatric disorders
Mania	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/39 (2.6%)
Dyspnoea	1/39 (2.6%)
Hiccups	1/39 (2.6%)
Lung disorder	1/39 (2.6%)
Pulmonary embolism	2/39 (5.1%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	1/39 (2.6%)
Vascular disorders
Aortic thrombosis	1/39 (2.6%)
Phlebitis	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Dovitinib
	Affected / at Risk (%)	# Events
Total	36/39 (92.3%)
Blood and lymphatic system disorders
Anaemia	6/39 (15.4%)
Neutropenia	3/39 (7.7%)
Thrombocytopenia	3/39 (7.7%)
Cardiac disorders
Tachicardia	2/39 (5.1%)
Ear and labyrinth disorders
Tinnitus	2/39 (5.1%)
Vertigo	3/39 (7.7%)
Eye disorders
Dry eye	2/39 (5.1%)
Keratitis	3/39 (7.7%)
Lacrimation increased	6/39 (15.4%)
Ocular hyperaemia	2/39 (5.1%)
Periorbital oedema	2/39 (5.1%)
Gastrointestinal disorders
Abdominal pain	11/39 (28.2%)
Abdominal pain upper	8/39 (20.5%)
Constipation	7/39 (17.9%)
Diarrhoea	28/39 (71.8%)
Dry mouth	6/39 (15.4%)
Dyspepsia	3/39 (7.7%)
Gastric disorder	3/39 (7.7%)
Haemorrhoids	3/39 (7.7%)
Nausea	17/39 (43.6%)
Stomatitis	2/39 (5.1%)
Toothache	2/39 (5.1%)
Vomiting	21/39 (53.8%)
Ascites	2/39 (5.1%)
General disorders
Asthenia	15/39 (38.5%)
Chest pain	4/39 (10.3%)
Fatigue	14/39 (35.9%)
Malaise	3/39 (7.7%)
Mucosal inflammation	4/39 (10.3%)
Oedema peripheral	3/39 (7.7%)
Pyrexia	7/39 (17.9%)
Hepatobiliary disorders
Hepatocellular injury	2/39 (5.1%)
Infections and infestations
Nasopharyngitis	2/39 (5.1%)
Urinary tract infection	2/39 (5.1%)
Investigations
Alanine aminotransferase increased	10/39 (25.6%)
Aspartate aminotransferase increased	11/39 (28.2%)
Blood alkaline phosphatase increased	13/39 (33.3%)
Blood bilirubin increased	4/39 (10.3%)
Blood calcium decreased	2/39 (5.1%)
Blood lactate dehydrogenase increased	3/39 (7.7%)
Blood triglycerides increased	2/39 (5.1%)
C-reactive protein increased	2/39 (5.1%)
Gamma-glutamyltransferase increased	14/39 (35.9%)
Lipase increased	4/39 (10.3%)
Protein total decreased	2/39 (5.1%)
Weight decreased	12/39 (30.8%)
Metabolism and nutrition disorders
Decreased appetite	15/39 (38.5%)
Dyslipidaemia	3/39 (7.7%)
Hypercholesterolaemia	4/39 (10.3%)
Hyperkalaemia	2/39 (5.1%)
Hypertriglyceridaemia	13/39 (33.3%)
Hypoalbuminaemia	7/39 (17.9%)
Hypocalcaemia	4/39 (10.3%)
Musculoskeletal and connective tissue disorders
Back pain	5/39 (12.8%)
Muscle spasms	3/39 (7.7%)
Musculoskeletal pain	4/39 (10.3%)
Musculoskeletal stiffness	2/39 (5.1%)
Myalgia	3/39 (7.7%)
Pain in extremity	7/39 (17.9%)
Nervous system disorders
Dysaesthesia	3/39 (7.7%)
Dysgeusia	6/39 (15.4%)
Headache	8/39 (20.5%)
Neuropathy peripheral	2/39 (5.1%)
Paraesthesia	6/39 (15.4%)
Sciatica	4/39 (10.3%)
Psychiatric disorders
Anxiety	3/39 (7.7%)
Insomnia	4/39 (10.3%)
Sleep disorder	2/39 (5.1%)
Renal and urinary disorders
Pollakiuria	4/39 (10.3%)
Proteinuria	4/39 (10.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/39 (5.1%)
Dysphonia	3/39 (7.7%)
Dyspnoea	7/39 (17.9%)
Epistaxis	4/39 (10.3%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	2/39 (5.1%)
Dermatitis allergic	2/39 (5.1%)
Dry skin	8/39 (20.5%)
Pruritus	2/39 (5.1%)
Rash	6/39 (15.4%)
Vascular disorders
Deep vein thrombosis	2/39 (5.1%)
Hypertension	13/39 (33.3%)
Hypotension	2/39 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.