A Randomized, Double-Blind, Phase 3 Study of Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced Pancreatic Cancer

• Register: EUCTR
• Last refreshed on: 21 November 2016
• Main ID: EUCTR2014-000294-39-AT
• Date of registration: 23/05/2014
• Prospective Registration: Yes
• Primary sponsor: Incyte Corporation
• Public title: A Randomized, Double-Blind, Phase 3 Study of Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced Pancreatic Cancer
• Scientific 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 2 Study) - The JANUS 2 Study
• Date of first enrolment: 17/06/2014
• Target sample size: 270
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000294-39
• 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

Argentina, Austria, Brazil, Chile, Colombia, Denmark, European Union, France, Ireland, Israel, Mexico, Netherlands, Peru, Portugal, Sweden, Switzerland, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Incyte

• Name: Clinical Trials Information
• Affiliation: Incyte

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 (CRP) > 10 mg/L and albumin = 35 g/L
- mGPS of 2: CRP > 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).
- Use of a fluoropyrimidine-containing regimen (eg, FOLFIRNOX,FOLFOX, CapeOx, chemoradiation, etc) in the first-line setting is
permitted provided the subject discontinued treatment for reasons other
than disease progression and the subject received = 8 weeks of therapy.
Subjects who received single-agent capecitabine as first-line therapy are
not eligible.
- Neoadjuvant regimens will be considered first-line therapy if the
subject has disease progression during treatment. Adjuvant regimens
will be considered first-line therapy if the subject has disease
progression during treatment or = 6 months after the last dose.
- There is no restriction on the use of fluoropyrimidine-containing
regimens in the neoadjuvant or adjuvant setting.
- 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 white blood cell count <
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 (use of biliary stent to achieve bilirubin
levels is permitted).
- 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.
- 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), per RECIST (v1.1).
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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

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 noninvasive or indolent malignancy without sponsor approval.
• Recent (= 3 months) history or ongoing partial or complete bowel
obstruction, unless surgically corrected.
• Prior severe reaction to fluoropyrimidines, known DPD deficiency, or
other known hypersensitivity to active substances, including fluorouracil
(5-FU), or ruxolitinib, or any of their excipients.
• Known history of human immunodeficiency virus 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

Advanced or metastatic adenocarcinoma of the pancreas in patients that have failed or are intolerant to first-line chemotherapy
MedDRA version: 18.0 Level: LLT Classification code 10033607 Term: Pancreatic cancer recurrent System Organ Class: 100000004864
MedDRA version: 18.0 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 100000004864
MedDRA version: 18.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864
MedDRA version: 18.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer 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
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

Trade Name: Capecitabine Actavis
Product Name: Capecitabine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Capecitabine Actavis
Product Name: Capecitabine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Capecitabine Accord
Product Name: Capecitabine Accord
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Capecitabine Accord
Product Name: Capecitabine Accord
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

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.

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

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.

Timepoint(s) of evaluation of this end point: The primary variable is OS, defined as number of days from randomization to death.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Progression-free survival, defined as the number of days from randomization to the earlier of death or disease progression by RECIST v1.1 criteria as assessed by the investigator.

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 incremented prior 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 adverse events and changes in safety assessments including
laboratory parameters.

Secondary ID(s)

2014-000294-39-SE

INCB18424-363

Source(s) of Monetary Support

Incyte Corporation