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Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer

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: NCT01528345
Recruitment Status : Terminated (Slow and low enrollment)
First Posted : February 8, 2012
Results First Posted : July 11, 2016
Last Update Posted : July 11, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Drug: Dovitinib
Drug: Fulvestrant
Drug: Dovitinib Placebo
Enrollment 97
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description Fulvestrant in combination with the study drug Dovitinib. Fulvestrant in combination with a placebo matching Dovitinib.
Period Title: Overall Study
Started 47 50
Completed 0 0
Not Completed 47 50
Reason Not Completed
Adverse Event             10             1
Death             1             1
Non-compliance with study treatment             1             0
Progressive Disease             26             40
Study Terminated by Sponsor             4             8
Subject/Guardian Decision             5             0
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo Total
Hide Arm/Group Description Fulvestrant in combination with the study drug Dovitinib. Fulvestrant in combination with a placebo matching Dovitinib. Total of all reporting groups
Overall Number of Baseline Participants 47 50 97
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants 50 participants 97 participants
63.5  (9.02) 61.7  (9.51) 62.6  (9.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 50 participants 97 participants
Female
47
 100.0%
50
 100.0%
97
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Progression Free Survival (PFS) Based on Local Investigator Assessment
Hide Description PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause and was assessed based on RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: 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; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.
Time Frame Every 8 weeks assessed up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they wereassigned at randomization.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 47 50
Median (95% Confidence Interval)
Unit of Measure: Months
All patients (n: 30, 34)
5.5
(3.8 to 14.0)
5.5
(3.5 to 10.7)
FGF amplified patients (n: 9, 9)
10.9
(3.5 to 16.5)
5.5
(3.5 to 16.4)
FGF non-amplified patients (n: 21, 25)
5.5
(3.8 to 16.8)
5.5
(1.9 to 12.8)
2.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: 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; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.
Time Frame Every 8 weeks assessed up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 47 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
All patients
27.7
(15.6 to 42.6)
10.0
(3.3 to 21.8)
FGF amplified patients
20.0
(4.3 to 48.1)
12.5
(1.6 to 38.3)
FGF non-amplified patients
31.3
(16.1 to 50.0)
8.8
(1.9 to 23.7)
3.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as time from the date of the first documented response (CR or PR) to the date of the first documented or death due to disease. If a patient does not have a progression event, DOR will be censored on the date of the last adequate tumor assessment.
Time Frame From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not analyzed as the study was terminated before duration of response could be analyzed.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Overall Survival (OS) Using Kaplan- Meier Method
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.
Time Frame From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 47 50
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(18.6 to NA)
25.9 [1] 
(18.4 to NA)
[1]
N/A = Not estimable as there were too few events (not enough patients died by the data cutoff date for database lock).
5.Secondary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety
Hide Description

The type, frequency and severity of adverse events, laboratory values, and Electrocardiograms (ECGs) experienced by patients will be assessed according to Common Terminology Criteria for Adverse Events.

The study enrollment was terminated early due to challenges in enrolling patients with FGF amplified status. See safety section for safety details.
Time Frame Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: Consisted of all patients who received at least one dose of any compound of the study treatment (dovitinib +fulvestrant or placebo+fulvestrant). Patients were analyzed according to the actual study treatment received. Actual treatment received was defined as the treatment the patient received at the first day of study medication.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 47 50
Measure Type: Number
Unit of Measure: Participants
47 50
6.Secondary Outcome
Title Time to Worsening of ECOG Performance Status
Hide Description Eastern Cooperative Oncology Group (ECOG) Performance Status (scales and criteria used by doctors and researchers to assess how a patient's disease is progressing and assess how the disease affects the daily living abilities of the patient.)
Time Frame Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not analyzed as the study was terminated before time to worsening ECOG performance could be analyzed.
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description:
Fulvestrant in combination with the study drug Dovitinib.
Fulvestrant in combination with a placebo matching Dovitinib.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Hide Arm/Group Description Fulvestrant in combination with the study drug Dovitinib. Fulvestrant in combination with a placebo matching Dovitinib.
All-Cause Mortality
Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   14/47 (29.79%)   10/50 (20.00%) 
Blood and lymphatic system disorders     
THROMBOCYTOPENIA † 1  1/47 (2.13%)  0/50 (0.00%) 
Cardiac disorders     
PERICARDIAL EFFUSION † 1  1/47 (2.13%)  0/50 (0.00%) 
Gastrointestinal disorders     
CONSTIPATION † 1  0/47 (0.00%)  1/50 (2.00%) 
DIARRHOEA † 1  0/47 (0.00%)  1/50 (2.00%) 
LUMBAR HERNIA † 1  1/47 (2.13%)  0/50 (0.00%) 
OESOPHAGEAL VARICES HAEMORRHAGE † 1  1/47 (2.13%)  0/50 (0.00%) 
PANCREATITIS † 1  0/47 (0.00%)  1/50 (2.00%) 
VARICES OESOPHAGEAL † 1  1/47 (2.13%)  0/50 (0.00%) 
General disorders     
DEVICE BREAKAGE † 1  0/47 (0.00%)  1/50 (2.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION † 1  1/47 (2.13%)  0/50 (0.00%) 
HYPERPYREXIA † 1  0/47 (0.00%)  1/50 (2.00%) 
NON-CARDIAC CHEST PAIN † 1  0/47 (0.00%)  1/50 (2.00%) 
Hepatobiliary disorders     
BILE DUCT OBSTRUCTION † 1  0/47 (0.00%)  1/50 (2.00%) 
HYPERBILIRUBINAEMIA † 1  1/47 (2.13%)  0/50 (0.00%) 
Infections and infestations     
INFECTION † 1  1/47 (2.13%)  0/50 (0.00%) 
PNEUMONIA † 1  1/47 (2.13%)  0/50 (0.00%) 
TOOTH ABSCESS † 1  0/47 (0.00%)  1/50 (2.00%) 
Injury, poisoning and procedural complications     
FEMUR FRACTURE † 1  0/47 (0.00%)  1/50 (2.00%) 
Metabolism and nutrition disorders     
DEHYDRATION † 1  1/47 (2.13%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders     
ARTHRITIS † 1  1/47 (2.13%)  0/50 (0.00%) 
BONE PAIN † 1  1/47 (2.13%)  0/50 (0.00%) 
SPINAL PAIN † 1  0/47 (0.00%)  1/50 (2.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
CERVIX CARCINOMA † 1  1/47 (2.13%)  0/50 (0.00%) 
MALIGNANT MELANOMA † 1  0/47 (0.00%)  1/50 (2.00%) 
Nervous system disorders     
ISCHAEMIC CEREBRAL INFARCTION † 1  1/47 (2.13%)  0/50 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
LARYNGOSPASM † 1  0/47 (0.00%)  1/50 (2.00%) 
PLEURAL EFFUSION † 1  1/47 (2.13%)  1/50 (2.00%) 
PULMONARY EMBOLISM † 1  3/47 (6.38%)  1/50 (2.00%) 
Skin and subcutaneous tissue disorders     
PIGMENTATION DISORDER † 1  1/47 (2.13%)  0/50 (0.00%) 
Vascular disorders     
DEEP VEIN THROMBOSIS † 1  2/47 (4.26%)  0/50 (0.00%) 
HYPERTENSIVE CRISIS † 1  0/47 (0.00%)  1/50 (2.00%) 
HYPOTENSION † 1  0/47 (0.00%)  1/50 (2.00%) 
PERIPHERAL ARTERY THROMBOSIS † 1  1/47 (2.13%)  0/50 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fulvestrant + Dovitinib Active Fulvestrant + Dovitinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   47/47 (100.00%)   45/50 (90.00%) 
Blood and lymphatic system disorders     
ANAEMIA † 1  9/47 (19.15%)  4/50 (8.00%) 
LEUKOPENIA † 1  3/47 (6.38%)  0/50 (0.00%) 
NEUTROPENIA † 1  7/47 (14.89%)  0/50 (0.00%) 
Ear and labyrinth disorders     
EAR PAIN † 1  5/47 (10.64%)  0/50 (0.00%) 
VERTIGO † 1  6/47 (12.77%)  0/50 (0.00%) 
Eye disorders     
DRY EYE † 1  5/47 (10.64%)  0/50 (0.00%) 
LACRIMATION INCREASED † 1  6/47 (12.77%)  0/50 (0.00%) 
VISION BLURRED † 1  3/47 (6.38%)  0/50 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION † 1  4/47 (8.51%)  3/50 (6.00%) 
ABDOMINAL PAIN † 1  8/47 (17.02%)  5/50 (10.00%) 
ABDOMINAL PAIN UPPER † 1  10/47 (21.28%)  3/50 (6.00%) 
CONSTIPATION † 1  8/47 (17.02%)  5/50 (10.00%) 
DIARRHOEA † 1  37/47 (78.72%)  15/50 (30.00%) 
DRY MOUTH † 1  5/47 (10.64%)  1/50 (2.00%) 
DYSPEPSIA † 1  12/47 (25.53%)  0/50 (0.00%) 
GASTRITIS † 1  3/47 (6.38%)  0/50 (0.00%) 
NAUSEA † 1  34/47 (72.34%)  11/50 (22.00%) 
STOMATITIS † 1  10/47 (21.28%)  2/50 (4.00%) 
VOMITING † 1  27/47 (57.45%)  4/50 (8.00%) 
General disorders     
ASTHENIA † 1  18/47 (38.30%)  11/50 (22.00%) 
FATIGUE † 1  16/47 (34.04%)  13/50 (26.00%) 
INFLUENZA LIKE ILLNESS † 1  3/47 (6.38%)  2/50 (4.00%) 
MALAISE † 1  4/47 (8.51%)  1/50 (2.00%) 
OEDEMA PERIPHERAL † 1  3/47 (6.38%)  3/50 (6.00%) 
PAIN † 1  4/47 (8.51%)  0/50 (0.00%) 
PYREXIA † 1  6/47 (12.77%)  5/50 (10.00%) 
Infections and infestations     
CONJUNCTIVITIS † 1  3/47 (6.38%)  3/50 (6.00%) 
NASOPHARYNGITIS † 1  3/47 (6.38%)  1/50 (2.00%) 
URINARY TRACT INFECTION † 1  2/47 (4.26%)  4/50 (8.00%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED † 1  15/47 (31.91%)  5/50 (10.00%) 
ASPARTATE AMINOTRANSFERASE INCREASED † 1  10/47 (21.28%)  4/50 (8.00%) 
BLOOD ALKALINE PHOSPHATASE INCREASED † 1  11/47 (23.40%)  1/50 (2.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1  9/47 (19.15%)  4/50 (8.00%) 
LIPASE INCREASED † 1  3/47 (6.38%)  3/50 (6.00%) 
WEIGHT DECREASED † 1  7/47 (14.89%)  3/50 (6.00%) 
WEIGHT INCREASED † 1  1/47 (2.13%)  3/50 (6.00%) 
Metabolism and nutrition disorders     
DECREASED APPETITE † 1  13/47 (27.66%)  8/50 (16.00%) 
HYPERGLYCAEMIA † 1  3/47 (6.38%)  1/50 (2.00%) 
HYPERKALAEMIA † 1  3/47 (6.38%)  2/50 (4.00%) 
HYPERTRIGLYCERIDAEMIA † 1  8/47 (17.02%)  1/50 (2.00%) 
HYPOCALCAEMIA † 1  3/47 (6.38%)  1/50 (2.00%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA † 1  7/47 (14.89%)  9/50 (18.00%) 
BACK PAIN † 1  7/47 (14.89%)  9/50 (18.00%) 
BONE PAIN † 1  3/47 (6.38%)  4/50 (8.00%) 
MUSCLE SPASMS † 1  3/47 (6.38%)  1/50 (2.00%) 
MUSCULAR WEAKNESS † 1  4/47 (8.51%)  0/50 (0.00%) 
MUSCULOSKELETAL PAIN † 1  4/47 (8.51%)  3/50 (6.00%) 
MYALGIA † 1  5/47 (10.64%)  1/50 (2.00%) 
PAIN IN EXTREMITY † 1  9/47 (19.15%)  3/50 (6.00%) 
SPINAL PAIN † 1  3/47 (6.38%)  1/50 (2.00%) 
Nervous system disorders     
AGEUSIA † 1  3/47 (6.38%)  0/50 (0.00%) 
DIZZINESS † 1  4/47 (8.51%)  2/50 (4.00%) 
DYSGEUSIA † 1  15/47 (31.91%)  1/50 (2.00%) 
HEADACHE † 1  17/47 (36.17%)  3/50 (6.00%) 
PARAESTHESIA † 1  2/47 (4.26%)  3/50 (6.00%) 
SYNCOPE † 1  5/47 (10.64%)  0/50 (0.00%) 
Psychiatric disorders     
INSOMNIA † 1  6/47 (12.77%)  4/50 (8.00%) 
Respiratory, thoracic and mediastinal disorders     
COUGH † 1  7/47 (14.89%)  6/50 (12.00%) 
DYSPNOEA † 1  8/47 (17.02%)  6/50 (12.00%) 
OROPHARYNGEAL PAIN † 1  3/47 (6.38%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders     
ALOPECIA † 1  4/47 (8.51%)  1/50 (2.00%) 
DERMATITIS ACNEIFORM † 1  3/47 (6.38%)  0/50 (0.00%) 
DRY SKIN † 1  9/47 (19.15%)  2/50 (4.00%) 
PRURITUS † 1  3/47 (6.38%)  2/50 (4.00%) 
RASH † 1  16/47 (34.04%)  3/50 (6.00%) 
Vascular disorders     
HOT FLUSH † 1  4/47 (8.51%)  3/50 (6.00%) 
HYPERTENSION † 1  13/47 (27.66%)  4/50 (8.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[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.
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01528345    
Other Study ID Numbers: CTKI258A2210
2011-001230-42 ( EudraCT Number )
First Submitted: January 31, 2012
First Posted: February 8, 2012
Results First Submitted: April 1, 2016
Results First Posted: July 11, 2016
Last Update Posted: July 11, 2016