Trial Outcomes & Findings for Randomized Trial of Fulvestrant With or Without Dasatinib in Men and Postmenopausal Women Who Have Hormone Receptor-positive Advanced Breast Cancer Previously Treated With an Aromatase Inhibitor (NCT NCT00754325)

Last Updated: 2016-05-26

Results Overview

This endpoint evaluated the progression free survival (PFS) of participants amongst the total evaluable population. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Participants with no recorded post-baseline tumor assessment had PFS censored at the day of randomization. Participants lost to follow-up were censored at the last date of contact. Participants that had not progressed or died had PFS censored at the date of last follow-up.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Results posted on

2016-05-26

Participant Flow

Study started September 2008 and completed January 2014; 9 participants chose to remain on active treatment after the study completed.

100 participants were enrolled and 100 participants were randomized (50 to each arm). 99 were treated (50 with fulvestrant + dasatinib and 49 with single-agent fulvestrant). Reason for non-treatment is that there was 1 withdrawal by participant.

Participant milestones

Participant milestones
Measure	Fulvestrant and Dasatinib Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Initial Treatment STARTED	50	49
Initial Treatment COMPLETED	0	0
Initial Treatment NOT COMPLETED	50	49
Progression and Cross-over STARTED	0	21
Progression and Cross-over COMPLETED	0	0
Progression and Cross-over NOT COMPLETED	0	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Fulvestrant and Dasatinib Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Initial Treatment Continuing Active Treatment	4	5
Initial Treatment Adverse Event	7	6
Initial Treatment Withdrawal by Subject	2	2
Initial Treatment Physician Decision	2	0
Initial Treatment Sponsor Request	0	1
Initial Treatment Disease Progression	35	35

Baseline Characteristics

Randomized Trial of Fulvestrant With or Without Dasatinib in Men and Postmenopausal Women Who Have Hormone Receptor-positive Advanced Breast Cancer Previously Treated With an Aromatase Inhibitor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fulvestrant and Dasatinib n=50 Participants Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=50 Participants Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.	Total n=100 Participants Total of all reporting groups
Age, Continuous	62.5 years STANDARD_DEVIATION 12.3 • n=5 Participants	61.4 years STANDARD_DEVIATION 10.3 • n=7 Participants	62.0 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	49 Participants n=7 Participants	99 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants	50 participants n=7 Participants	100 participants n=5 Participants

PRIMARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Population: Evaluable population on initial treatment; all treated participants with measurable disease at baseline and at least one on-study tumor assessment. Participants without tumor response assessment due to rapid progression or study drug toxicity included as non-responders. Censored participants = 15 Fulvestrant and Dasatinib, 9 Fulvestrant

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Number of Participants With Disease Progression (PD) or Death	35 participants	40 participants

SECONDARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Progression free survival (PFS) was defined as the time in months from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Median Time of Progression-free Survival (PFS)	5.6 months Interval 3.6 to 9.3	5.3 months Interval 3.0 to 7.4

SECONDARY outcome

Timeframe: at 6 months

PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 6 months after randomization. Progression free survival (PFS) was defined as the time from randomization to either the date the subject was first recorded as having PD (even if the subject went off treatment because of toxicity), or the date of death if the subject died due to any causes before progression. Progression=At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan Meier assessments were used to estimate the percentages.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Percentage of Participants With Progression Free Survival (PFS) at 6 Months	48.1 percentage of participants Interval 33.0 to 61.7	44.6 percentage of participants Interval 30.1 to 58.1

SECONDARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Clinical benefit rate (CBR) was defined as the percentage of participants that had Stable Disease (SD), complete response (CR), or partial response (PR) for greater than or equal to 6 months if there was no evidence of progression at or before assessment performed on or after Study Day 161. CR= Disappearance of all target lesions. No new lesions. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Physical examination, radiological assessment, and bone scans (if applicable) were used to assess outcome.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Percentage of Participants With Clinical Benefit for At Least 6 Months	38.0 percentage of participants Interval 24.7 to 52.8	42.9 percentage of participants Interval 28.8 to 57.8

SECONDARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Table represents the best response achieved over this time frame. CR = Disappearance of all target lesions. No new lesions. PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest sum LD since the treatment started. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) Complete Response, CR	0 participants	0 participants
Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) Partial Response, PR	1 participants	3 participants
Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) Stable Disease, SD	34 participants	28 participants
Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) Disease Progression, PD	11 participants	16 participants
Number of Participants With Complete Response (CR) , Partial Response (PR), Stable Disease (SD), and Disease Progression (PD) Not Evaluable	4 participants	2 participants

SECONDARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Population: Evaluable population on initial treatment with measurable lesion by RECIST (Response Evaluation Criteria In Solid Tumors). Participants without tumor response assessment due to rapid progression or study drug toxicity included in population as non-responders.

Best overall response rate (ORR) = number of participants with measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) having a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. RECIST 1.1 response criteria applies. To be recorded as best response, CR or PR had to be confirmed at ≥ 4 weeks interval. An unconfirmed CR was recorded as PR.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=31 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=37 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Number of Participants With Best Overall Response	1 participants	2 participants

SECONDARY outcome

Timeframe: Date of randomization to date of initial disease progression, or date of death (whichever occurs first), up to January 2014 (approximately 5 years)

Population: Safety Population on initial treatment; any participants that was randomized to any treatment group in the study and received at least one treatment therapy.

Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Outcome measures

Outcome measures
Measure	Fulvestrant and Dasatinib n=50 Participants Arm 1: Participants in this group received a drug regimen that consisted of both fulvestrant and dasatinib. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years. Dasatinib: Tablets, Oral, 100 mg, once daily (QD), up to 2 years	Fulvestrant n=49 Participants Arm 2: Participants in this group received a drug regimen that consisted of fulvestrant only. Fulvestrant: Intramuscular injection (IM), loading dose (500 mg) on Day 1 followed by 500 mg on Day 15 of Cycle 1 (28-day cycle). In subsequent cycles, 500 mg IM administered on Day 1, up to 2 years.
Number of Participants With Serious Adverse Events, Death, and Discontinuation Due to Adverse Events Serious Adverse Events	14 participants	11 participants
Number of Participants With Serious Adverse Events, Death, and Discontinuation Due to Adverse Events Deaths	15 participants	16 participants
Number of Participants With Serious Adverse Events, Death, and Discontinuation Due to Adverse Events Discontinued due to AEs	7 participants	6 participants

Adverse Events

Fulvestrant and Dasatinib

Serious events: 14 serious events

Other events: 48 other events

Deaths: 0 deaths

Fulvestrant

Serious events: 11 serious events

Other events: 44 other events

Deaths: 0 deaths

Fulvestrant Crossover to Fulvestrant and Dasatinib

Serious events: 7 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER