CTKI258A2210

Novartis Pharma AG

CH-4002, Basel, Switzerland,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,

No

No

No

Final

03 Apr 2015

No

Yes

03 Apr 2015

Yes

To assess the treatment effect of dovitinib in combination with fulvestrant vs. fulvestrant plus placebo on progression-free survival (PFS) per local Investigator assessment in patients with HER2-, HR+, LA/mBC that have evidence of disease progression on or after prior endocrine therapy for each of the 2 groups, namely: - FGF Pathway amplified - Regardless of FGF pathway amplification status

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

19 Apr 2012

No

Yes

Argentina: 8

Austria: 4

Belgium: 10

Brazil: 1

France: 16

Hungary: 9

Italy: 13

Netherlands: 4

Russian Federation: 5

Spain: 3

Taiwan: 7

United States: 17

97

59

0

0

0

0

0

0

52

45

0

Overall Study (overall period)

Randomised - controlled

Yes

Dovitinib

TKI258

Tablet

Oral use

Active Dovitinib (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule

Fulvestrant

Solution for injection

Intramuscular use

Fulvestrant (in solution) injected intramuscularly at a dose of 500 mg once on Week 1 Day 1, Week 3 Day 1 and Week 5 Day 1 and subsequently once every 4 weeks on Day 1 of the week.

Dovitinib Placebo

Tablet

Oral use

Dovitinib Placebo (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule

Fulvestrant + Dovitinib active

Fulvestrant + Dovitinib placebo

Fulvestrant + Dovitinib active

Fulvestrant + Dovitinib placebo

Efficacy criteria were therefore achieved in FGF amplified patients. In consideration of the smaller than planned number of events (only 18 events against the planned 50 events) results are to be interpreted with caution as only indicative and requiring further exploration. For the FGF non-amplified patients, where the target number of PFS events was achieved, the study passed the futility analysis (i.e. dovitinib plus fulvestrant treatment was not rejected as futile).

Primary

Every 8 weeks assessed up to 34 months

Fulvestrant + Dovitinib placebo v Fulvestrant + Dovitinib active

97

Pre-specified

0.681

2-sided

ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST. 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.

Secondary

Every 8 weeks assessed up to 34 months

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. This outcome measure was not analyzed as the study was terminated before duration of response could be analyzed.

Secondary

From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months

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. The Upper Limit of confidence interval is not estimable as there were too few events (not enough patients died by the data cutoff date for database lock). 99999.9 represents not applicable data and used as place holder to avoid system error because EudraCT system is not accepting "NA" for not available/not applicable data.

Secondary

From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months

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.

Secondary

Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)

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.) This outcome measure was not analyzed as the study was terminated before duration of response could be analyzed.

Secondary

Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.

Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.

18.0

Fulvestrant + Dovitinib placebo

Fulvestrant + Dovitinib active