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: 11 April 2016
• Main ID: EUCTR2014-000293-20-IT
• Date of registration: 23/06/2014
• Prospective Registration: Yes
• 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: 31/07/2014
• 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

Countries of recruitment

Australia, 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).
a.Use of a fluoropyrimidine-containing regimen (eg, FOLFIRNOX, FOLFOX, CapeOx, etc) in the first-line setting is permitted provided the subject discontinued treatment for reasons other than disease progression and the subject received = 2 cycles of therapy. Subjects who received single-agent capecitabine as first-line therapy are not eligible.
b. There is no restriction on the use of fluoropyrimidine-containing regimens in the neo-adjuvant or adjuvant setting.
c. History of palliative radiotherapy to disease sites is allowed provided there are other sites of disease or subsequent progression of the disease in the radiation field, and = 4 weeks have elapsed since the completion of radiotherapy and all treatment-related toxicities have resolved or are at a new stable baseline.

•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 (transfusions are permitted to achieve baseline hemoglobin level).
-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 measured or calculated by Cockroft-Gault equation or the estimated glomerular filtration rate (GFR) = 50 mL/min/1.73 m2 using the MDRD formula.
-ECOG performance status 0 to 2.
B-ody 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).
-Measurable lesions may be in the field of prior radiation; however, there must be at least a 4-week period between the last radiation treatment and demonstration of interval progression of the lesion compared with the baseline scan documenting disease status for the lesion to be considered measurable.
•Females are either postmenopausal for at least 1 year with documented follicle-stimulating hormone (FSH) > 30 IU/L, are surgically sterile for at least 3 months, or must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through follow-up if of childbearing potential. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed). For all females, the pregnancy test result must be negative at screening
Exclusion criteria:
• Received more than 1 prior chemotherapy regimen 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 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, radiation therapy administered within 30 days of enrollment, or prior history of radiation therapy to = 25% of the bone marrow
•Subjects who received palliative radiation treatment to a limited field or on an accelerated schedule within the last 30 days are eligible for enrollment, provided at least 7 days have elapsed from completion of radiation therapy prior to the first dose and all treatment related toxicities have resolved or are at a new stable baseline.
•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 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 noninvasive 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 sensitivity to 5-FU.
•Known history of human immunodeficiency virus (HIV) infection.
•Active hepatitis B or C infection that requires treatment.
•Unwilling to be transfused with blood components.
•Pregnant or breastfeeding women.
•Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.
•Any condition in the judgment of the investigator that would jeopardize the safety of the subject or compliance with the protocol.


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

Health Condition(s) or Problem(s) studied

Male or female, 18 years or older with histologically or cytologically confirmed adenocarcinoma of the pancreas that is inoperable or metastatic.
MedDRA version: 17.0 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 100000004864
MedDRA version: 17.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864

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

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: (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3- cyclopentylpropanenitrile phosphate
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

Trade Name: Capecitabine Actavis
Product Name: Capecitabine
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
CAS Number: 1158798-73-3
Current Sponsor code: N/A
Other descriptive name: N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
INN or Proposed INN: Capecitabine
CAS Number: 1158798-73-3
Current Sponsor code: N/A
Other descriptive name: N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

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.

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.

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

Secondary Outcome(s)

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 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.

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.

Secondary ID(s)

INCB18424-362

Source(s) of Monetary Support

Incyte Corporation