Trial Outcomes & Findings for Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer (NCT NCT01528345)
NCT ID: NCT01528345
Last Updated: 2016-07-11
Results Overview
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.
TERMINATED
PHASE2
97 participants
Every 8 weeks assessed up to 34 months
2016-07-11
Participant Flow
Participant milestones
| Measure |
Fulvestrant + Dovitinib Active
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
50
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
47
|
50
|
Reasons for withdrawal
| Measure |
Fulvestrant + Dovitinib Active
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
1
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Non-compliance with study treatment
|
1
|
0
|
|
Overall Study
Progressive Disease
|
26
|
40
|
|
Overall Study
Study Terminated by Sponsor
|
4
|
8
|
|
Overall Study
Subject/Guardian Decision
|
5
|
0
|
Baseline Characteristics
Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer
Baseline characteristics by cohort
| Measure |
Fulvestrant + Dovitinib Active
n=47 Participants
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 Participants
Fulvestrant in combination with a placebo matching Dovitinib.
|
Total
n=97 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.5 Years
STANDARD_DEVIATION 9.02 • n=5 Participants
|
61.7 Years
STANDARD_DEVIATION 9.51 • n=7 Participants
|
62.6 Years
STANDARD_DEVIATION 9.27 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 8 weeks assessed up to 34 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Fulvestrant + Dovitinib Active
n=47 Participants
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 Participants
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Progression Free Survival (PFS) Based on Local Investigator Assessment
All patients (n: 30, 34)
|
5.5 Months
Interval 3.8 to 14.0
|
5.5 Months
Interval 3.5 to 10.7
|
|
Progression Free Survival (PFS) Based on Local Investigator Assessment
FGF amplified patients (n: 9, 9)
|
10.9 Months
Interval 3.5 to 16.5
|
5.5 Months
Interval 3.5 to 16.4
|
|
Progression Free Survival (PFS) Based on Local Investigator Assessment
FGF non-amplified patients (n: 21, 25)
|
5.5 Months
Interval 3.8 to 16.8
|
5.5 Months
Interval 1.9 to 12.8
|
SECONDARY outcome
Timeframe: Every 8 weeks assessed up to 34 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Fulvestrant + Dovitinib Active
n=47 Participants
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 Participants
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Overall Response Rate (ORR)
All patients
|
27.7 Percentage of participants
Interval 15.6 to 42.6
|
10.0 Percentage of participants
Interval 3.3 to 21.8
|
|
Overall Response Rate (ORR)
FGF amplified patients
|
20.0 Percentage of participants
Interval 4.3 to 48.1
|
12.5 Percentage of participants
Interval 1.6 to 38.3
|
|
Overall Response Rate (ORR)
FGF non-amplified patients
|
31.3 Percentage of participants
Interval 16.1 to 50.0
|
8.8 Percentage of participants
Interval 1.9 to 23.7
|
SECONDARY outcome
Timeframe: From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 monthsPopulation: This outcome measure was not analyzed as the study was terminated before duration of response could be analyzed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From date of randomization to date of death from any cause whichever comes first, assessed up to 34 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Fulvestrant + Dovitinib Active
n=47 Participants
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 Participants
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Overall Survival (OS) Using Kaplan- Meier Method
|
NA Months
Interval 18.6 to
N/A = Not estimable as there were too few events (not enough patients died by the data cutoff date for database lock).
|
25.9 Months
Interval 18.4 to
N/A = Not estimable as there were too few events (not enough patients died by the data cutoff date for database lock).
|
SECONDARY outcome
Timeframe: Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)Population: 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.
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.
Outcome measures
| Measure |
Fulvestrant + Dovitinib Active
n=47 Participants
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 Participants
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety
|
47 Participants
|
50 Participants
|
SECONDARY outcome
Timeframe: Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)Population: This outcome measure was not analyzed as the study was terminated before time to worsening ECOG performance could be analyzed.
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.)
Outcome measures
Outcome data not reported
Adverse Events
Fulvestrant + Dovitinib Active
Fulvestrant + Dovitinib Placebo
Serious adverse events
| Measure |
Fulvestrant + Dovitinib Active
n=47 participants at risk
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 participants at risk
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
2.1%
1/47
|
0.00%
0/50
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
2.1%
1/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/47
|
2.0%
1/50
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/47
|
2.0%
1/50
|
|
Gastrointestinal disorders
LUMBAR HERNIA
|
2.1%
1/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
OESOPHAGEAL VARICES HAEMORRHAGE
|
2.1%
1/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.00%
0/47
|
2.0%
1/50
|
|
Gastrointestinal disorders
VARICES OESOPHAGEAL
|
2.1%
1/47
|
0.00%
0/50
|
|
General disorders
DEVICE BREAKAGE
|
0.00%
0/47
|
2.0%
1/50
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
2.1%
1/47
|
0.00%
0/50
|
|
General disorders
HYPERPYREXIA
|
0.00%
0/47
|
2.0%
1/50
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/47
|
2.0%
1/50
|
|
Hepatobiliary disorders
BILE DUCT OBSTRUCTION
|
0.00%
0/47
|
2.0%
1/50
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
2.1%
1/47
|
0.00%
0/50
|
|
Infections and infestations
INFECTION
|
2.1%
1/47
|
0.00%
0/50
|
|
Infections and infestations
PNEUMONIA
|
2.1%
1/47
|
0.00%
0/50
|
|
Infections and infestations
TOOTH ABSCESS
|
0.00%
0/47
|
2.0%
1/50
|
|
Injury, poisoning and procedural complications
FEMUR FRACTURE
|
0.00%
0/47
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
2.1%
1/47
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
2.1%
1/47
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
2.1%
1/47
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
SPINAL PAIN
|
0.00%
0/47
|
2.0%
1/50
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CERVIX CARCINOMA
|
2.1%
1/47
|
0.00%
0/50
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA
|
0.00%
0/47
|
2.0%
1/50
|
|
Nervous system disorders
ISCHAEMIC CEREBRAL INFARCTION
|
2.1%
1/47
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
LARYNGOSPASM
|
0.00%
0/47
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
2.1%
1/47
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
6.4%
3/47
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
PIGMENTATION DISORDER
|
2.1%
1/47
|
0.00%
0/50
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
4.3%
2/47
|
0.00%
0/50
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.00%
0/47
|
2.0%
1/50
|
|
Vascular disorders
HYPOTENSION
|
0.00%
0/47
|
2.0%
1/50
|
|
Vascular disorders
PERIPHERAL ARTERY THROMBOSIS
|
2.1%
1/47
|
0.00%
0/50
|
Other adverse events
| Measure |
Fulvestrant + Dovitinib Active
n=47 participants at risk
Fulvestrant in combination with the study drug Dovitinib.
|
Fulvestrant + Dovitinib Placebo
n=50 participants at risk
Fulvestrant in combination with a placebo matching Dovitinib.
|
|---|---|---|
|
Infections and infestations
NASOPHARYNGITIS
|
6.4%
3/47
|
2.0%
1/50
|
|
Infections and infestations
URINARY TRACT INFECTION
|
4.3%
2/47
|
8.0%
4/50
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
31.9%
15/47
|
10.0%
5/50
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
21.3%
10/47
|
8.0%
4/50
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
23.4%
11/47
|
2.0%
1/50
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
19.1%
9/47
|
8.0%
4/50
|
|
Investigations
LIPASE INCREASED
|
6.4%
3/47
|
6.0%
3/50
|
|
Investigations
WEIGHT DECREASED
|
14.9%
7/47
|
6.0%
3/50
|
|
Investigations
WEIGHT INCREASED
|
2.1%
1/47
|
6.0%
3/50
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
27.7%
13/47
|
16.0%
8/50
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
6.4%
3/47
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
6.4%
3/47
|
4.0%
2/50
|
|
Metabolism and nutrition disorders
HYPERTRIGLYCERIDAEMIA
|
17.0%
8/47
|
2.0%
1/50
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
6.4%
3/47
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
14.9%
7/47
|
18.0%
9/50
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
14.9%
7/47
|
18.0%
9/50
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
6.4%
3/47
|
8.0%
4/50
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
6.4%
3/47
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
8.5%
4/47
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
8.5%
4/47
|
6.0%
3/50
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
10.6%
5/47
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
19.1%
9/47
|
6.0%
3/50
|
|
Musculoskeletal and connective tissue disorders
SPINAL PAIN
|
6.4%
3/47
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
14.9%
7/47
|
12.0%
6/50
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
17.0%
8/47
|
12.0%
6/50
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
6.4%
3/47
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
8.5%
4/47
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM
|
6.4%
3/47
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
19.1%
9/47
|
4.0%
2/50
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
6.4%
3/47
|
4.0%
2/50
|
|
Skin and subcutaneous tissue disorders
RASH
|
34.0%
16/47
|
6.0%
3/50
|
|
Vascular disorders
HOT FLUSH
|
8.5%
4/47
|
6.0%
3/50
|
|
Vascular disorders
HYPERTENSION
|
27.7%
13/47
|
8.0%
4/50
|
|
Nervous system disorders
AGEUSIA
|
6.4%
3/47
|
0.00%
0/50
|
|
Nervous system disorders
DIZZINESS
|
8.5%
4/47
|
4.0%
2/50
|
|
Nervous system disorders
DYSGEUSIA
|
31.9%
15/47
|
2.0%
1/50
|
|
Nervous system disorders
HEADACHE
|
36.2%
17/47
|
6.0%
3/50
|
|
Nervous system disorders
PARAESTHESIA
|
4.3%
2/47
|
6.0%
3/50
|
|
Nervous system disorders
SYNCOPE
|
10.6%
5/47
|
0.00%
0/50
|
|
Psychiatric disorders
INSOMNIA
|
12.8%
6/47
|
8.0%
4/50
|
|
Gastrointestinal disorders
DYSPEPSIA
|
25.5%
12/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
GASTRITIS
|
6.4%
3/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
NAUSEA
|
72.3%
34/47
|
22.0%
11/50
|
|
Gastrointestinal disorders
STOMATITIS
|
21.3%
10/47
|
4.0%
2/50
|
|
Gastrointestinal disorders
VOMITING
|
57.4%
27/47
|
8.0%
4/50
|
|
General disorders
ASTHENIA
|
38.3%
18/47
|
22.0%
11/50
|
|
General disorders
FATIGUE
|
34.0%
16/47
|
26.0%
13/50
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
6.4%
3/47
|
4.0%
2/50
|
|
General disorders
MALAISE
|
8.5%
4/47
|
2.0%
1/50
|
|
General disorders
OEDEMA PERIPHERAL
|
6.4%
3/47
|
6.0%
3/50
|
|
General disorders
PAIN
|
8.5%
4/47
|
0.00%
0/50
|
|
General disorders
PYREXIA
|
12.8%
6/47
|
10.0%
5/50
|
|
Infections and infestations
CONJUNCTIVITIS
|
6.4%
3/47
|
6.0%
3/50
|
|
Blood and lymphatic system disorders
ANAEMIA
|
19.1%
9/47
|
8.0%
4/50
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
6.4%
3/47
|
0.00%
0/50
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
14.9%
7/47
|
0.00%
0/50
|
|
Ear and labyrinth disorders
EAR PAIN
|
10.6%
5/47
|
0.00%
0/50
|
|
Ear and labyrinth disorders
VERTIGO
|
12.8%
6/47
|
0.00%
0/50
|
|
Eye disorders
DRY EYE
|
10.6%
5/47
|
0.00%
0/50
|
|
Eye disorders
LACRIMATION INCREASED
|
12.8%
6/47
|
0.00%
0/50
|
|
Eye disorders
VISION BLURRED
|
6.4%
3/47
|
0.00%
0/50
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
8.5%
4/47
|
6.0%
3/50
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
17.0%
8/47
|
10.0%
5/50
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
21.3%
10/47
|
6.0%
3/50
|
|
Gastrointestinal disorders
CONSTIPATION
|
17.0%
8/47
|
10.0%
5/50
|
|
Gastrointestinal disorders
DIARRHOEA
|
78.7%
37/47
|
30.0%
15/50
|
|
Gastrointestinal disorders
DRY MOUTH
|
10.6%
5/47
|
2.0%
1/50
|
Additional Information
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER