Back to resultsRuxolitinib in Combination With Pemetrexed/Cisplatin in Non Small Cell Lung Cancer
Primary Purpose
NSCLC (Non-small Cell Lung Carcinoma)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Placebo
Pemetrexed
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for NSCLC (Non-small Cell Lung Carcinoma) focused on measuring Non small cell lung cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB Stage IV, or recurrent after prior definitive intervention (radiation, surgery, or chemoradiation therapy, with or without adjuvant or neoadjuvant chemotherapy).
- Radiographically measurable or evaluable disease.
- Life expectancy of at least 12 weeks.
- Tumor without activating driver mutations for which there is available therapy (eg, tumor without mutations in epidermal growth factor receptor or anaplastic lymphoma).
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
Criteria:
- C-reactive protein >10 mg/L AND albumin ≥35 g/L; Score = 1
- C-reactive protein >10 mg L AND albumin <35 g/L; Score = 2
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
Exclusion Criteria:
- Squamous or mixed histology (eg, adenosquamous) NSCLC
- Previous systemic therapy for advanced or metastatic disease.
- Known active central nervous system (CNS) metastases.
- Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
- Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment.
- Uncontrolled concomitant medical conditions, including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric diseases.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ruxolitinib plus Pemetrexed/Cisplatin
Placebo plus Pemetrexed/Cisplatin
Arm Description
Outcomes
Primary Outcome Measures
Overall Survival (OS)
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.
Secondary Outcome Measures
Progression-free Survival (PFS)
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.
Objective Response Rate (ORR)
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.
Duration of Response
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.
Participants With Treatment-emergent Adverse Events (TEAEs)
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02119650
Brief Title
Ruxolitinib in Combination With Pemetrexed/Cisplatin in Non Small Cell Lung Cancer
Official Title
A Randomized, Double-Blind Phase 2 Study of Ruxolitinib or Placebo in Combination With Pemetrexed/Cisplatin and Pemetrexed Maintenance for Initial Treatment of Subjects With Nonsquamous Non-Small Cell Lung Cancer That Is Stage IIIB, Stage IV, or Recurrent
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated as other related studies of ruxolitinib did not provide sufficient efficacy to warrant continuation.
Study Start Date
February 11, 2014 (Actual)
Primary Completion Date
February 11, 2016 (Actual)
Study Completion Date
June 21, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study was to determine if ruxolitinib, in combination with Pemetrexed/Cisplatin and Pemetrexed Maintenance, is safe and effective in the treatment of nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent.
Detailed Description
The study consisted of an open-label, safety run-in (consisting of 1 to 4 cohorts of 9 participants each), to confirm the safety of ruxolitinib in combination with pemetrexed/cisplatin in participants with nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent. Participants in the safety run-in received open-label ruxolitinib and pemetrexed and cisplatin.
In the second part of the study, participants enrolled and randomized and received pemetrexed and cisplatin (open-label) and either ruxolitinib or placebo in a blinded manner. The dose of ruxolitinib administered was determined from the data produced in the safety run-in phase.
Treatment consisted of repeating 21-day cycles. Participants received infusions of pemetrexed and cisplatin on Day 1 of each cycle and ruxolitinib/placebo was self-administered during the entire cycle. Maintenance therapy with ruxolitinib or placebo in combination with pemetrexed, based on the original treatment assignment, was allowed for participants eligible for maintenance therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC (Non-small Cell Lung Carcinoma)
Keywords
Non small cell lung cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib plus Pemetrexed/Cisplatin
Arm Type
Experimental
Arm Title
Placebo plus Pemetrexed/Cisplatin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi ®, Jakavi ®
Intervention Description
5 mg tablets to be administered by mouth at dose selected from safety run-in phase (Ruxolitinib 15 mg twice daily (BID))
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
5 mg matching placebo tablets to be administered by mouth
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
Alimta®
Intervention Description
500 mg/m^2 administered as an intravenous infusion over 10 minutes
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75 mg/m^2 infused over 2 hours beginning 30 ± 5 minutes after the end of the pemetrexed infusion
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
Randomization until death due to any cause; up to 16 months or data cutoff 11FEB2016.
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Randomization to disease progression, or death due to any cause if sooner; up to 16 months or to the data cutoff 11FEB2016.
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Baseline through end of study; up to 16 months or to the data cutoff 11FEB2016.
Title
Duration of Response
Description
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.
Time Frame
From the start of response to the end of response; up to 16 months or to the data cutoff 11FEB2016.
Title
Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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).
Time Frame
Baseline through approximately 30 days post treatment discontinuation; up to 16 months or to the data cutoff 11FEB2016.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB Stage IV, or recurrent after prior definitive intervention (radiation, surgery, or chemoradiation therapy, with or without adjuvant or neoadjuvant chemotherapy).
Radiographically measurable or evaluable disease.
Life expectancy of at least 12 weeks.
Tumor without activating driver mutations for which there is available therapy (eg, tumor without mutations in epidermal growth factor receptor or anaplastic lymphoma).
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
Criteria:
C-reactive protein >10 mg/L AND albumin ≥35 g/L; Score = 1
C-reactive protein >10 mg L AND albumin <35 g/L; Score = 2
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
Exclusion Criteria:
Squamous or mixed histology (eg, adenosquamous) NSCLC
Previous systemic therapy for advanced or metastatic disease.
Known active central nervous system (CNS) metastases.
Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
Current uncontrolled cardiac disease such as angina or myocardial infarction, congestive heart failure including New York Heart Association functional classification of 3, or arrhythmia requiring treatment.
Uncontrolled concomitant medical conditions, including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric diseases.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard T Kennealey, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Fayetteville
State/Province
Arkansas
Country
United States
City
Fresno
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Lone Tree
State/Province
Colorado
Country
United States
City
Norwich
State/Province
Connecticut
Country
United States
City
Southington
State/Province
Connecticut
Country
United States
City
Augusta
State/Province
Georgia
Country
United States
City
Joliet
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Lafayette
State/Province
Indiana
Country
United States
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Kansas City
State/Province
Kansas
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Reno
State/Province
Nevada
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
Mount Kisco
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
City
Canton
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Chattanooga
State/Province
Tennessee
Country
United States
City
Knoxville
State/Province
Tennessee
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Ogden
State/Province
Utah
Country
United States
City
Leesburg
State/Province
Virginia
Country
United States
City
Kennewick
State/Province
Washington
Country
United States
City
Seattle
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Ruxolitinib in Combination With Pemetrexed/Cisplatin in Non Small Cell Lung Cancer
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