Back to resultsA Study of Ruxolitinib in Pancreatic Cancer Patients
Primary Purpose
Pancreatic Cancer
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ruxolitinib
Placebo
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Metastatic pancreatic cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the pancreas.
- Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Received 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy).
- ≥ 2 weeks elapsed from the completion of previous treatment regimen and participants must have recovered or be at a new stable baseline from any related toxicities.
- Radiographically measurable or evaluable disease
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
Criteria:
- mGPS of 1: C-reactive protein (CRP) > 10 mg/L and albumin ≥ 35 g/L
- mGPS of 2: CRP > 10 mg/L and albumin < 35 g/L
Exclusion Criteria:
- Received more than 1 prior regimen for advanced or metastatic disease.
- Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment
- Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
- Current or previous other malignancy within 2 years of study entry without sponsor approval
- Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency (DPD), or other known hypersensitivity to active substances, including fluorouracil (5-FU), ruxolitinib, or any of their excipients.
- Prior treatment with a JAK inhibitor for any indication.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ruxolitinib plus capecitabine
Placebo plus capecitabine
Arm Description
Outcomes
Primary Outcome Measures
Overall Survival (OS)
Overall survival is reported here based on the number of deaths from randomization until the data cut-off.
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 LD recorded since the treatment started or the appearance of one or more new lesions, unequivocal progression of non-target lesions, or the appearance of new lesions.
Percentage of Participants Achieving 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 at least a 20% increase in the sum of the 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, unequivocal progression of non-target lesions, or the appearance of new lesions.
Objective Response Rate (ORR)
Objective response rate determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumours RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by RECIST at any post baseline visit. Per 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
Duration of overall response was defined as the time in months from Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) until the first date Progressive Disease (PD) was objectively documented or until the date of death. Per 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.
Participants With Treatment-Emergent Adverse Events (TEAEs)
A treatment-emergent AE was defined as an event occurring after exposure to at least 1 dose of study drug (ruxolitinib or placebo). 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
NCT02119663
Brief Title
A Study of Ruxolitinib in Pancreatic Cancer Patients
Official Title
A Randomized, Double-Blind, Phase 3 Study of the JAK 1/2 Inhibitor Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced or Metastatic Adenocarcinoma of the Pancreas Who Have Failed or Are Intolerant to First-Line Chemotherapy (The JANUS 2 Study)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
The safety committee found no safety issues but recommended halting the study based on a lack of efficacy in a similar trial. The sponsor terminated the trial.
Study Start Date
June 2014 (Actual)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
October 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
This was to determine the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of metastatic pancreatic cancer.
Detailed Description
This was a randomized, double-blinded, placebo-controlled, Phase 3 study, in which approximately 270 participants with advanced or metastatic adenocarcinoma of the pancreas who had failed or were intolerant to first-line chemotherapy were to be randomized (1:1) to one of the following treatment groups:
Treatment A (N = 135): Capecitabine + ruxolitinib
Treatment B (N = 135): Capecitabine + placebo
Treatment consisted of repeating 21-day cycles. Capecitabine was self-administered for the first 14 days of each cycle, and ruxolitinib/placebo was self-administered during the entire cycle. Treatment for all participants was to continue as long as the regimen was tolerated, and the participant did not meet discontinuation criteria. Participants who discontinued treatment continued to be followed for subsequent anticancer treatments and survival.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Metastatic pancreatic cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib plus capecitabine
Arm Type
Experimental
Arm Title
Placebo plus capecitabine
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 twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
5 mg matching placebo tablets to be administered by mouth twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
150 mg or 500 mg tablets to be administered by mouth twice daily (BID)
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival is reported here based on the number of deaths from randomization until the data cut-off.
Time Frame
Randomization until death due to any cause up to 6-months or to the 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 LD recorded since the treatment started or the appearance of one or more new lesions, unequivocal progression of non-target lesions, or the appearance of new lesions.
Time Frame
Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
Title
Percentage of Participants Achieving 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 at least a 20% increase in the sum of the 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, unequivocal progression of non-target lesions, or the appearance of new lesions.
Time Frame
Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
Title
Objective Response Rate (ORR)
Description
Objective response rate determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumours RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by RECIST at any post baseline visit. Per 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 6-months or to the data cutoff 11FEB2016.
Title
Duration of Response
Description
Duration of overall response was defined as the time in months from Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) until the first date Progressive Disease (PD) was objectively documented or until the date of death. Per 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 6-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 after exposure to at least 1 dose of study drug (ruxolitinib or placebo). 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 6-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 adenocarcinoma of the pancreas.
Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Received 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy).
≥ 2 weeks elapsed from the completion of previous treatment regimen and participants must have recovered or be at a new stable baseline from any related toxicities.
Radiographically measurable or evaluable disease
An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
Criteria:
mGPS of 1: C-reactive protein (CRP) > 10 mg/L and albumin ≥ 35 g/L
mGPS of 2: CRP > 10 mg/L and albumin < 35 g/L
Exclusion Criteria:
Received more than 1 prior regimen for advanced or metastatic disease.
Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment
Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
Current or previous other malignancy within 2 years of study entry without sponsor approval
Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency (DPD), or other known hypersensitivity to active substances, including fluorouracil (5-FU), ruxolitinib, or any of their excipients.
Prior treatment with a JAK inhibitor for any indication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fitzroy Dawkins, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
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Huntsville
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Wein
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Vitacura
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Bogota
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Medellin
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Naestved
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Odense C
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Dubin
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Haifa
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Petach Tikva
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Ramat Gan
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Linköping
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Uppsala
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Bellinzona
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Geneve
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Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
29508247
Citation
Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. doi: 10.1007/s10637-018-0580-2. Epub 2018 Mar 6.
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A Study of Ruxolitinib in Pancreatic Cancer Patients
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