A randomized, double-blind, study of ruxolitinib or placebo in combination with capecitabine as second line treatent for Subjects With Pancreatic cancer (The JANUS 1 Study)

• Register: EUCTR
• Last refreshed on: 10 April 2017
• Main ID: EUCTR2014-000293-20-GB
• Date of registration: 24/11/2014
• Prospective Registration: No
• Primary sponsor: Incyte Corporation
• Public title: A randomized, double-blind, study of ruxolitinib or placebo in combination with capecitabine as second line treatent for Subjects With Pancreatic cancer (The JANUS 1 Study)
• Scientific title: INCB 18424-362 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) - The JANUS 1 Study
• Date of first enrolment: 11/07/2014
• Target sample size: 310
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000293-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, European Union, Italy, Korea, Republic of, New Zealand, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Incyte Corporation

• Name: Clinical Trials Information
• Affiliation: Incyte Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
•Male or female, 18 years or older.
•Histologically or cytologically confirmed adenocarcinoma of the pancreas.
•Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
•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
•Received 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy).

•Able to tolerate and benefit from therapy as evidenced by:
Absolute neutrophil count = 1.5 × 109/L with WBC < 20 × 109/L.
Platelets = 75 × 109/L.
Hemoglobin = 9 g/dL
Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 2.5 × upper limit of normal (ULN); or = 5 × ULN in the presence of liver metastases.
Total bilirubin = 1.5 × ULN; if total bilirubin is > 1.5 × ULN then direct bilirubin must be = 1.5 × ULN.
Alkaline phosphatase < 3 × ULN.
Lactate dehydrogenase (LDH) < 3 × ULN in the absence of hemolysis.
Creatinine clearance = 50 mL/min
ECOG performance status 0 to 2.
Body mass index (BMI) > 16 kg/m2.
Absence of significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease.
Able to swallow and retain oral medication.
•= 2 weeks elapsed from the completion of previous treatment regimen and subjects must have recovered or be at a new stable baseline from any related toxicities.
•Radiographically measurable or evaluable disease (based on local evaluation).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170

Exclusion criteria:
• Received more than 1 prior regimen (eg, chemotherapy, biologic, targeted, immune, investigational therapies alone or in combination) for advanced or metastatic disease.
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
• Known brain or central nervous system metastases or history of uncontrolled seizures.
• Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy.
• Ongoing radiation therapy or 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).
• Subjects who participated in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to the first dose.
• 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 non-invasive or indolent malignancy without sponsor approval.
• Recent (= 3 months) history or ongoing partial or complete bowel obstruction, unless due to the disease understudy and surgically corrected.
• Prior severe reaction to fluoropyrimidines, known DPD deficiency, or other known hypersensitivity to active substances, including fluorouracil (5-FU), ruxolitinib, or any of their excipients.
• Known history of human immunodeficiency virus (HIV) infection.
• Active hepatitis B or C infection that requires treatment.
• Unwilling to be transfused with blood components.
• Prior treatment with a JAK inhibitor for any indication.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Male or female, 18 years or older with histologically or cytologically confirmed adenocarcinoma of the pancreas that is inoperable or metastatic.
MedDRA version: 17.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 100000004864
MedDRA version: 17.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864

Intervention(s)

Trade Name: Jakafi
Product Name: ruxolitinib
Product Code: INCB018424
Pharmaceutical Form: Tablet
INN or Proposed INN: ruxolitinib
CAS Number: 941678-49-5
Current Sponsor code: INCB018424
Other descriptive name: (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To evaluate and compare the efficacy of the 2 treatment groups with respect to PFS.
To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response.
To evaluate and compare the safety and tolerability of ruxolitinib in combination with capecitabine versus capecitabine alone.

Primary end point(s): Overall survival as determined from the date of randomization until death due to any cause.

Main Objective: To evaluate and compare the OS of subjects with advanced or metastatic adenocarcinoma of the pancreas when treated with ruxolitinib in combination with capecitabine versus capecitabine alone.

Timepoint(s) of evaluation of this end point: This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.

Secondary Outcome(s)

Secondary end point(s): • Progression-free survival defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause, if sooner.
• Restricted mean survival time (RMST) estimated over the interval between the date of randomization and 12 months (365 days); if the last death in either treatment group is prior to study Day 365, then the earlier of the death in the placebo or the death in the ruxolitinib treatment group, truncated to the last full 30-day increment prior to the earlier death, will be used as the end of the RMST estimation interval in both groups.
• Objective response rate and duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment.
• Safety and tolerability of the treatment regimens through assessment of AEs and changes in safety assessments including laboratory parameters.

Timepoint(s) of evaluation of this end point: This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.

Secondary ID(s)

2014-000293-20-IT

INCB18424-362

Source(s) of Monetary Support

Incyte Corporation