Clinical Trials Register

Summary
EudraCT Number:	2014-000294-39
Sponsor's Protocol Code Number:	INCB18424-363
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-07-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2014-000294-39

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

The JANUS 2 Study

A.4.1

Sponsor's protocol code number

INCB18424-363

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Incyte Corporation
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Incyte Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Incyte
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Rt 141 & Henry Clay Road
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19880
B.5.3.4	Country	United States
B.5.5	Fax number	13024252734
B.5.6	E-mail	RegAffairs@incyte.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Jakafi
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Corporation
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ruxolitinib
D.3.2	Product code	INCB018424
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ruxolitinib
D.3.9.2	Current sponsor code	INCB018424
D.3.9.3	Other descriptive name	(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
D.3.9.4	EV Substance Code	SUB31642
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Capecitabine Actavis
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis Group PTC ehf
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Capecitabine
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Capecitabine
D.3.9.3	Other descriptive name	CAPECITABINE
D.3.9.4	EV Substance Code	SUB12474MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	150 to 500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced or metastatic adenocarcinoma of the pancreas in patients that have failed or are intolerant to first-line chemotherapy

E.1.1.1

Medical condition in easily understood language

Advanced pancreatic cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10033607
E.1.2	Term	Pancreatic cancer recurrent
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10033606
E.1.2	Term	Pancreatic cancer non-resectable
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10033605
E.1.2	Term	Pancreatic cancer metastatic
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10033604
E.1.2	Term	Pancreatic cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

•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.

E.2.2

Secondary objectives of the trial

•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.

E.2.3

Trial contains a sub-study

E.3

Principal 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, 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.
•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 or the estimated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula.
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).

E.4

Principal 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 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 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 sensitivity to fluorouracil (5-FU).
•Known history of human immunodeficiency virus infection.
•Active hepatitis B or C infection that requires treatment.
•Unwilling to be transfused with blood components.

E.5 End points

E.5.1

Primary end point(s)

•Overall survival as determined from the date of randomization until death due to any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary variable is OS, defined as number of days from randomization to death.

E.5.2

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 0 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 and 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 AEs and changes in safety assessments including laboratory parameters.

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

Chile

Colombia

European Union

Israel

Mexico

Peru

Switzerland

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

There is no predefined EOT.
After discontinuation of study treatment, all subjects will remain in the follow-up phase of the study for the collection of subsequent anticancer therapies and survival

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

270

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-10-14

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