Trial Outcomes & Findings for Ruxolitinib in Patients With Breast Cancer (NCT NCT01562873)

Last Updated: 2017-02-23

Results Overview

The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).

Results posted on

2017-02-23

Participant Flow

Patients enrolled from October 2012 through June 2014.

Patients must have had sufficient archival specimen for central pStat3 testing to be eligible.

Participant milestones

Participant milestones
Measure	Ruxolitinib-Cohort A Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).	Ruxolitinib-Cohort B Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Overall Study STARTED	21	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	21	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ruxolitinib-Cohort A Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).	Ruxolitinib-Cohort B Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Overall Study Disease Progression per RECIST	10	0
Overall Study Adverse Event	1	0
Overall Study Clinical Disease Progression	9	0
Overall Study Clinical PD and adverse event	1	0

Baseline Characteristics

Ruxolitinib in Patients With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruxolitinib-Cohort A n=21 Participants Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Age, Continuous	51 years n=5 Participants
Gender Female	21 Participants n=5 Participants
Gender Male	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants
pStat3 Positive Status moderate to high positive	21 participants n=5 Participants
pStat3 Positive Status low positive	0 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).

Population: The analysis dataset is comprised all enrolled patients.

Outcome measures

Outcome measures
Measure	Ruxolitinib-Cohort A n=21 Participants Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Objective Response Rate	0.0 proportion of patients Interval 0.0 to 0.133

SECONDARY outcome

Population: The analysis dataset is comprised all enrolled patients.

Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration.

Outcome measures

Outcome measures
Measure	Ruxolitinib-Cohort A n=21 Participants Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Clinical Benefit Rate	0.0 proportion of patients Interval 0.0 to 0.133

SECONDARY outcome

Timeframe: In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).

Population: The analysis dataset is comprised all enrolled patients.

Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

Outcome measures

Outcome measures
Measure	Ruxolitinib-Cohort A n=21 Participants Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Overall Survival	4.5 months Interval 2.9 to 10.2

SECONDARY outcome

Timeframe: Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).

Population: The analysis dataset is comprised all enrolled patients.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Ruxolitinib-Cohort A n=21 Participants Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Progression-Free Survival	1.2 months Interval 0.97 to 1.84

Adverse Events

Ruxolitinib-Cohort A

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ruxolitinib-Cohort A n=21 participants at risk Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Blood and lymphatic system disorders Anemia	9.5% 2/21 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Investigations Aspartate aminotransferase increased	9.5% 2/21 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Investigations GGT increased	4.8% 1/21 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Investigations Neutrophil count decreased	9.5% 2/21 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.

Other adverse events

Other adverse events
Measure	Ruxolitinib-Cohort A n=21 participants at risk Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity. Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of \>/=5 by central testing or Cohort B - low positive status defined as a score of 3-4. Each cohort was evaluated with a 2 stage design. Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
Blood and lymphatic system disorders BL101	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Gastrointestinal disorders GI108	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Gastrointestinal disorders GI123	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Gastrointestinal disorders GI179	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Gastrointestinal disorders GI216	40.0% 2/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
General disorders CN101	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
General disorders CN105	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
General disorders CN108	60.0% 3/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
General disorders CN109	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Infections and infestations IN999	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Investigations IV129	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Investigations IV137	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Musculoskeletal and connective tissue disorders MU112	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Musculoskeletal and connective tissue disorders MU999	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Nervous system disorders NE145	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Respiratory, thoracic and mediastinal disorders PU113	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Respiratory, thoracic and mediastinal disorders PU114	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.
Skin and subcutaneous tissue disorders DE999	20.0% 1/5 • Assessed each cycle throughout the 12 cycles of treatment and at time of off-treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. Other AEs were defined as events with treatment attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4.

Additional Information

Nancy Lin, MD

Dana-Farber Cancer Institute

Phone: 617.632.2335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place