Study of Ruxolitinib in Pancreatic Cancer Patients (Janus 1)

Study Overview
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Brief Summary
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Determining the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of advanced or metastatic pancreatic cancer.

Detailed Description
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This was a randomized, double-blinded, placebo-controlled, Phase 3 study, in which approximately 310 participants with advanced or metastatic adenocarcinoma of the pancreas who have failed, or were intolerant to first-line chemotherapy, were to be randomized (1:1) to one of the following treatment groups: Treatment A (N = 155): Capecitabine + ruxolitinib Treatment B (N = 155): 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 daily for each cycle. Treatment for all participants continued as long as the regimen was tolerated, and the participant did not meet discontinuation criteria. Participants who discontinued study treatment before study termination were monitored for safety up to 30-35 days from the end of treatment. All participants were followed for survival until study termination or the safety follow-up visit.

Official Title
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A Randomized, Double-Blind, Phase 3 Study of the JAK1/2 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 1 Study)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Placebo
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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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 Modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below: mGPS of 1: C-reactive protein >10 mg/L and albumin ≥35 g/L mGPS of 2: C-reactive protein >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). Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency (DPD), or other known hypersensitivity to active substances, including fluorouracil (5-FU), or ruxolitinib, or any of their excipients. Prior treatment with a JAK inhibitor for any indication.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib plus capecitabine<br> | Drug: Ruxolitinib<br>* 5 mg tablets to be administered by mouth twice daily (BID)<br>* Other names: Jakavi ®;Drug: Capecitabine<br>* 150 and 500 mg tablets to be administered by mouth twice daily (BID)<br>|
| Active Comparator: Placebo plus capecitabine<br> | Drug: Placebo<br>* 5 mg tablets to be administered by mouth twice daily (BID)<br>Drug: Capecitabine<br>* 150 and 500 mg tablets to be administered by mouth twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival is reported here based on the number of deaths from randomization up to 6-months or to the data cutoff 11FEB2016. | Randomization until death due to any cause; up to the data cutoff 11FEB2016. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | 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. | Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016. | 
| 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. | Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016. | 
| 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. | Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016. | 
| 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. | Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016. | 
| 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). | Baseline through approximately 30 days post treatment discontinuation; up to 6-months or to the data cutoff 11FEB2016. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic pancreatic cancer, Metastatic pancreatic adenocarcinoma that is recurrent