Trial Outcomes & Findings for A Clinical Trial to Compare Efficacy and Tolerability of Fulvestrant 250mg, 250mg (Plus 250mg Loading Regimen) and 500mg (NCT NCT00305448)
NCT ID: NCT00305448
Last Updated: 2012-02-15
Results Overview
An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response. Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization
COMPLETED
PHASE2
143 participants
baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008)
2012-02-15
Participant Flow
Postmenopausal women with oestrogen receptor positive advanced breast cancer progressing or relapsing after previousendocrine therapy were randomized between 7th March 2006 and 4th September 2007. The trial was conducted in Japan only. One patient randomised to Fulvestrant 500mg was not dosed, so the Safety population has 46 patients for that arm.
8 of the 151 enrolled patients were not randomized to treatment groups for the following reasons - 8 patients were incorrectly enrolled (ie did not comply with one or more inclusion / exclusion criteria).
Participant milestones
| Measure |
Fulvestrant 250 mg
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
Fulvestrant 500 mg
|
|---|---|---|---|
|
Overall Study
STARTED
|
45
|
51
|
47
|
|
Overall Study
COMPLETED
|
14
|
17
|
14
|
|
Overall Study
NOT COMPLETED
|
31
|
34
|
33
|
Reasons for withdrawal
| Measure |
Fulvestrant 250 mg
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
Fulvestrant 500 mg
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
|
Overall Study
Disease Progression
|
27
|
31
|
28
|
|
Overall Study
Subjective Disease Progression
|
1
|
2
|
2
|
|
Overall Study
Tumor Marker Elevation
|
0
|
0
|
1
|
Baseline Characteristics
A Clinical Trial to Compare Efficacy and Tolerability of Fulvestrant 250mg, 250mg (Plus 250mg Loading Regimen) and 500mg
Baseline characteristics by cohort
| Measure |
Fulvestrant 250 mg
n=45 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 Participants
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=47 Participants
Fulvestrant 500 mg
|
Total
n=143 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
62.5 Years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
62.4 Years
STANDARD_DEVIATION 9.5 • n=7 Participants
|
62.7 Years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
62.5 Years
STANDARD_DEVIATION 8.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
143 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline and every 12 weeks (+/- 2weeks) from randomization data up to data cut-off (19th march 2008)An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response. Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization
Outcome measures
| Measure |
Fulvestrant 250 mg
n=45 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 Participants
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=47 Participants
Fulvestrant 500 mg
|
|---|---|---|---|
|
Objective Response Rate (ORR)
|
11.1 percentage of participants
|
17.6 percentage of participants
|
10.6 percentage of participants
|
SECONDARY outcome
Timeframe: every 12 weeks from randomization (+/- 2 weeks) until data cut-off (19th march 2008)Time (in days) from randomization until objective disease progression or death (in the absence of objective progression). RECIST tumour assessments carried out every 12 weeks from randomization (+/- 2 weeks) until data cut-off on 19th March 2008.
Outcome measures
| Measure |
Fulvestrant 250 mg
n=45 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 Participants
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=47 Participants
Fulvestrant 500 mg
|
|---|---|---|---|
|
Time to Progression (TTP)
|
169 days
Interval 30.0 to 508.0
|
211 days
Interval 0.0 to 426.0
|
169 days
Interval 0.0 to 590.0
|
SECONDARY outcome
Timeframe: RECIST tumour assessments carried out every 12 weeks from randomisation (+/- 2 weeks) until data cut-off on19th March 2008.Time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who achieved a confirmed Complete Response or confirmed Partial Response.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: every 12 weeks(+/- 2 weeks) from randomization to data up to data cut-off, 19th March 2008.A Clinical Benefit (CB) responder is defined as a patient having a best overall response of Complete response (CR), Partial Response (PR) or Stable disease (SD) provided SD (or better) was present = 154 days from randomization (ie SD = 24 weeks with the 2 week RECIST assessment time window allowed). The Clinical Benefit Rate is the percentage of patients with CB.
Outcome measures
| Measure |
Fulvestrant 250 mg
n=45 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 Participants
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=47 Participants
Fulvestrant 500 mg
|
|---|---|---|---|
|
Clinical Benefit Rate (CBR)
|
42.2 percentage of participants
|
54.9 percentage of participants
|
46.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to 12 weeksPopulation: Patients who agreed to participate in the PK substudy. The results are based on 148, 122 and 140 plasma-concentration records from patients in the 250 mg, 250 mg + LD and 500 mg treatment arms respectively.
The measure of dispersion for mean population clearance is based on the estimated inter-individual variance
Outcome measures
| Measure |
Fulvestrant 250 mg
n=70 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
Fulvestrant 500 mg
|
|---|---|---|---|
|
Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body
|
34.4 L/h
Standard Deviation 0.096
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 12 weeksPopulation: Patients who agreed to participate in the PK substudy.
The measure of dispersion for volume of distribution is based on the inter-individual variance estimated for the apparent volume of plasma into which Fulvestrant distributes
Outcome measures
| Measure |
Fulvestrant 250 mg
n=70 Participants
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
Fulvestrant 500 mg
|
|---|---|---|---|
|
Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes
|
35300 Vss/F (L)
Standard Deviation 0.175
|
—
|
—
|
Adverse Events
Fulvestrant 250 mg
Fulvestrant 250 mg + Loading Dose
Fulvestrant 500 mg
Serious adverse events
| Measure |
Fulvestrant 250 mg
n=45 participants at risk
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 participants at risk
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=46 participants at risk
Fulvestrant 500 mg
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
|
Nervous system disorders
Brain Stem Infarction
|
2.2%
1/45
|
0.00%
0/51
|
0.00%
0/46
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
|
Gastrointestinal disorders
Diverticular Perforation
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
|
Nervous system disorders
Dizziness
|
0.00%
0/45
|
0.00%
0/51
|
2.2%
1/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fallopian Tube Cancer
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
|
Infections and infestations
Herpes Zoster
|
2.2%
1/45
|
0.00%
0/51
|
0.00%
0/46
|
|
Nervous system disorders
Optic Neuritis
|
0.00%
0/45
|
2.0%
1/51
|
0.00%
0/46
|
Other adverse events
| Measure |
Fulvestrant 250 mg
n=45 participants at risk
Fulvestrant 250 mg
|
Fulvestrant 250 mg + Loading Dose
n=51 participants at risk
Fulvestrant 250 mg + Loading Dose
|
Fulvestrant 500 mg
n=46 participants at risk
Fulvestrant 500 mg
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.7%
3/45
|
3.9%
2/51
|
4.3%
2/46
|
|
Metabolism and nutrition disorders
Anorexia
|
4.4%
2/45
|
7.8%
4/51
|
6.5%
3/46
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.4%
2/45
|
13.7%
7/51
|
4.3%
2/46
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
6.7%
3/45
|
9.8%
5/51
|
6.5%
3/46
|
|
Gastrointestinal disorders
Constipation
|
8.9%
4/45
|
13.7%
7/51
|
10.9%
5/46
|
|
Injury, poisoning and procedural complications
Contusion
|
2.2%
1/45
|
5.9%
3/51
|
6.5%
3/46
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.4%
2/45
|
5.9%
3/51
|
2.2%
1/46
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
4/45
|
3.9%
2/51
|
2.2%
1/46
|
|
General disorders
Fatigue
|
15.6%
7/45
|
13.7%
7/51
|
15.2%
7/46
|
|
Nervous system disorders
Headache
|
6.7%
3/45
|
15.7%
8/51
|
8.7%
4/46
|
|
Vascular disorders
Hot Flush
|
17.8%
8/45
|
21.6%
11/51
|
15.2%
7/46
|
|
Vascular disorders
Hypertension
|
8.9%
4/45
|
0.00%
0/51
|
0.00%
0/46
|
|
Nervous system disorders
Hypoaesthesia
|
2.2%
1/45
|
5.9%
3/51
|
4.3%
2/46
|
|
General disorders
Injection Site Erythema
|
6.7%
3/45
|
3.9%
2/51
|
2.2%
1/46
|
|
General disorders
Injection Site Induration
|
20.0%
9/45
|
11.8%
6/51
|
21.7%
10/46
|
|
General disorders
Injection Site Pain
|
31.1%
14/45
|
21.6%
11/51
|
30.4%
14/46
|
|
General disorders
Injection Site Pruritus
|
8.9%
4/45
|
3.9%
2/51
|
8.7%
4/46
|
|
Psychiatric disorders
Insomnia
|
8.9%
4/45
|
5.9%
3/51
|
2.2%
1/46
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.9%
4/45
|
3.9%
2/51
|
2.2%
1/46
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
4.4%
2/45
|
5.9%
3/51
|
2.2%
1/46
|
|
Infections and infestations
Nasopharyngitis
|
37.8%
17/45
|
29.4%
15/51
|
34.8%
16/46
|
|
Gastrointestinal disorders
Nausea
|
24.4%
11/45
|
17.6%
9/51
|
13.0%
6/46
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
3/45
|
2.0%
1/51
|
4.3%
2/46
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/45
|
0.00%
0/51
|
6.5%
3/46
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.4%
2/45
|
5.9%
3/51
|
8.7%
4/46
|
|
General disorders
Pyrexia
|
4.4%
2/45
|
7.8%
4/51
|
10.9%
5/46
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.2%
1/45
|
5.9%
3/51
|
4.3%
2/46
|
|
Nervous system disorders
Somnolence
|
6.7%
3/45
|
2.0%
1/51
|
2.2%
1/46
|
|
Gastrointestinal disorders
Stomatitis
|
4.4%
2/45
|
5.9%
3/51
|
10.9%
5/46
|
|
Ear and labyrinth disorders
Vertigo
|
2.2%
1/45
|
0.00%
0/51
|
6.5%
3/46
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/45
|
5.9%
3/51
|
6.5%
3/46
|
|
Investigations
Weight Decreased
|
6.7%
3/45
|
2.0%
1/51
|
2.2%
1/46
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60