Trial Outcomes & Findings for Ruxolitinib in Combination With Pemetrexed/Cisplatin in Non Small Cell Lung Cancer (NCT NCT02119650)

NCT ID: NCT02119650

Last Updated: 2018-02-13

Results Overview

Overall survival is defined as the time from randomization to death due to any cause. Participants without death observed at the time of the analysis were censored at last date known to be alive. The median overall survival time was estimated using the Kaplan-Meier method. Overall survival was compared between treatment groups using log-rank test.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

Randomization until death due to any cause; up to 16 months or data cutoff 11FEB2016.

Results posted on

2018-02-13

Participant Flow

This study was conducted at 42 study centers (25 in the United States, 4 in Spain, 3 in France, 3 in Portugal, 2 in Denmark, 2 in Germany, 2 in Italy, 1 in the Netherlands).

Participant milestones

Participant milestones
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin Ruxolitinib was self-administered as a 15 mg twice daily (BID) oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Overall Study STARTED	39	37
Overall Study COMPLETED	14	11
Overall Study NOT COMPLETED	25	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin Ruxolitinib was self-administered as a 15 mg twice daily (BID) oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Overall Study Adverse Event	3	4
Overall Study Subject decision	2	3
Overall Study Disease progression	11	14
Overall Study Death	5	1
Overall Study Noncompliance with study treatment	1	1
Overall Study Study terminated by the sponsor	1	0
Overall Study Physician Decision	0	2
Overall Study Multiple reasons for termination	2	1

Baseline Characteristics

Ruxolitinib in Combination With Pemetrexed/Cisplatin in Non Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=39 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=37 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Total n=76 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 8.85 • n=5 Participants	62.0 years STANDARD_DEVIATION 8.55 • n=7 Participants	61.8 years STANDARD_DEVIATION 8.65 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Body Mass Index (BMI)	27.67 kg/m^2 STANDARD_DEVIATION 6.402 • n=5 Participants	27.65 kg/m^2 STANDARD_DEVIATION 7.26 • n=7 Participants	27.66 kg/m^2 STANDARD_DEVIATION 6.787 • n=5 Participants

PRIMARY outcome

Timeframe: Randomization until death due to any cause; up to 16 months or data cutoff 11FEB2016.

Population: The intent-to-treat (ITT) population consisted of participants that were randomized in the study.

Outcome measures

Outcome measures
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=39 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=37 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Overall Survival (OS)	7.5 months Interval 5.7 to Not evaluable due to insufficient number of participants with events.	5.9 months Interval 4.0 to Not evaluable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Randomization to disease progression, or death due to any cause if sooner; up to 16 months or to the data cutoff 11FEB2016.

Population: The intent-to-treat (ITT) population consisted of participants that were randomized in the study.

PFS is defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause if sooner. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum Longest Diameter (LD) recorded since the treatment started or the appearance of one or more new lesions, unequivocal progression of non-target lesions or increase in disease burden for subjects with only nonmeasurable disease.

Outcome measures

Outcome measures
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=39 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=37 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Progression-free Survival (PFS)	NA Months Progression-free Survival (PFS) was not conducted due to early termination of the study and insufficient number of participants with events.	NA Months Progression-free Survival (PFS) was not conducted due to early termination of the study and insufficient number of participants with events.

SECONDARY outcome

Timeframe: Baseline through end of study; up to 16 months or to the data cutoff 11FEB2016.

Population: The intent-to-treat (ITT) population consisted of participants that were randomized in the study.

Objective response rate determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) at any post baseline visit. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) : Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions with no worsening of non-target lesions and no new lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=39 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=37 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Objective Response Rate (ORR) Overall Response	12 Participants	13 Participants
Objective Response Rate (ORR) Complete Response	0 Participants	0 Participants
Objective Response Rate (ORR) Partial Response	12 Participants	13 Participants
Objective Response Rate (ORR) Stable Disease	4 Participants	5 Participants
Objective Response Rate (ORR) Progressive Disease	6 Participants	4 Participants
Objective Response Rate (ORR) Unable to Evaluate	2 Participants	3 Participants
Objective Response Rate (ORR) Not Assessed	15 Participants	12 Participants

SECONDARY outcome

Timeframe: From the start of response to the end of response; up to 16 months or to the data cutoff 11FEB2016.

Population: The intent-to-treat (ITT) population consisted of participants that were randomized in the study.

For objective responders, the duration of response is defined as the difference of the end of response and the start of response. The start of a response was the first visit where the subject achieves PR or better based on RECIST v1.1 criteria. The end of response was the first visit after PD based on RECIST v1.1 criteria.

Outcome measures

Outcome measures
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=12 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=13 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Duration of Response	20.14 weeks Interval 18.0 to 30.71	12.14 weeks Interval 6.0 to 24.0

SECONDARY outcome

Timeframe: Baseline through approximately 30 days post treatment discontinuation; up to 16 months or to the data cutoff 11FEB2016.

Population: The safety evaluable population consisted of all participants exposed to at least 1 dose of study drug.

A treatment-emergent AE was defined as an event occurring (or worsening of any pre-existing) after exposure to at least 1 dose of study drug. A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).

Outcome measures

Outcome measures
Measure	Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin n=39 Participants Ruxolitinib was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).	Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin n=37 Participants Matching placebo was self-administered as a 15 mg BID oral treatment during the randomized, double-blind treatment, without regard to food. Pemetrexed 500 mg/m\^2 was administered as an intravenous infusion over 10 minutes, and 75 mg/m\^2 Cisplatin was infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion on Day 1 of each 21-day cycle (Treatment Cycles).
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who had any TEAEs	39 Participants	36 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who had treatment-related TEAEs	16 Participants	28 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any serious TEAE	19 Participants	16 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who had Grade 3 or higher TEAEs	25 Participants	22 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants with a fatal TEAE	4 Participants	4 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) TEAEs related to reference therapy	30 Participants	35 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who were hospitalized due to TEAEs	16 Participants	15 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who discontinued drug due to TEAEs	2 Participants	4 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants who interrupted drug due to TEAEs	11 Participants	15 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Discontinued reference therapy due to TEAEs	4 Participants	7 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Interrupted reference therapy due to TEAEs	8 Participants	7 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Participants given concomitant meds due to TEAEs	36 Participants	32 Participants
Participants With Treatment-emergent Adverse Events (TEAEs) Procedure/nondrug therapy due to TEAEs	17 Participants	12 Participants

Adverse Events

Double-Blind Treatment: Ruxolitinib + Pemetrexed/Cisplatin

Serious events: 19 serious events

Other events: 37 other events

Deaths: 0 deaths

Double-Blind Treatment: Placebo Plus Pemetrexed/Cisplatin

Serious events: 16 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 855 463-3463

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER