Brief Summary
Determining the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of advanced or metastatic pancreatic cancer.
Brief Title
Study of Ruxolitinib in Pancreatic Cancer Patients (Janus 1)
Detailed Description
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.
* 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
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
* Modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
1. mGPS of 1: C-reactive protein \>10 mg/L and albumin ≥35 g/L
2. 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.
* 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:
1. mGPS of 1: C-reactive protein \>10 mg/L and albumin ≥35 g/L
2. 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.
Inclusion 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
* Modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:
1. mGPS of 1: C-reactive protein \>10 mg/L and albumin ≥35 g/L
2. mGPS of 2: C-reactive protein \>10 mg/L and albumin \<35 g/L
* 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:
1. mGPS of 1: C-reactive protein \>10 mg/L and albumin ≥35 g/L
2. mGPS of 2: C-reactive protein \>10 mg/L and albumin \<35 g/L
Gender
All
Gender Based
false
Keywords
Metastatic pancreatic cancer
Metastatic pancreatic adenocarcinoma that is recurrent
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02117479
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 18424-362
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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)
Primary Outcomes
Outcome Description
Overall survival is reported here based on the number of deaths from randomization up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Randomization until death due to any cause; up to the data cutoff 11FEB2016.
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Progression-free Survival (PFS)
Outcome 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.
Outcome Time Frame
Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Percentage of Participants Achieving Progression Free Survival (PFS)
Outcome 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.
Outcome Time Frame
Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Objective Response Rate (ORR)
Outcome 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.
Outcome Time Frame
Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Duration of Response
Outcome 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).
Outcome Time Frame
Baseline through approximately 30 days post treatment discontinuation; up to 6-months or to the data cutoff 11FEB2016.
Outcome Measure
Participants With Treatment-Emergent Adverse Events (TEAEs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jennifer Chuy
Investigator Email
jchuy@montefiore.org
Investigator Phone
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Endocrine System Cancers --- ENDOCRINE GLAND NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Endocrine System Cancers --- ENDOCRINE SYSTEM DISEASES
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
PANCREATIC NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
ENDOCRINE GLAND NEOPLASMS
DIGESTIVE SYSTEM DISEASES
PANCREATIC DISEASES
ENDOCRINE SYSTEM DISEASES
RUXOLITINIB
COUNTERFEIT DRUGS
CAPECITABINE
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
FLUOROURACIL
URACIL
PYRIMIDINONES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES