A Study of Ruxolitinib in Pancreatic Cancer Patients

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02119663
• Collaborator: (none)
• Enrollment: 86
• Locations: 95
• Arms: 2
• Actual Duration (Months): 28
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was to determine the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of metastatic pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Ruxolitinib; Drug: Placebo; Drug: Capecitabine	Phase 3

Detailed Description

This was a randomized, double-blinded, placebo-controlled, Phase 3 study, in which approximately 270 participants with advanced or metastatic adenocarcinoma of the pancreas who had failed or were intolerant to first-line chemotherapy were to be randomized (1:1) to one of the following treatment groups:

• Treatment A (N = 135): Capecitabine + ruxolitinib

• Treatment B (N = 135): 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 during the entire cycle. Treatment for all participants was to continue as long as the regimen was tolerated, and the participant did not meet discontinuation criteria. Participants who discontinued treatment continued to be followed for subsequent anticancer treatments and survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Phase 3 Study of the JAK 1/2 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)
• Actual Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ruxolitinib plus capecitabine	Drug: Ruxolitinib; 5 mg tablets to be administered by mouth twice daily (BID); Other Names: Jakafi ® Jakavi ® ; Drug: Capecitabine; 150 mg or 500 mg tablets to be administered by mouth twice daily (BID)
Active Comparator: Placebo plus capecitabine	Drug: Placebo; 5 mg matching placebo tablets to be administered by mouth twice daily (BID); Drug: Capecitabine; 150 mg or 500 mg tablets to be administered by mouth twice daily (BID)

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Randomization until death due to any cause up to 6-months or to the data cutoff 11FEB2016.]

   Overall survival is reported here based on the number of deaths from randomization until the data cut-off.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.]

   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 as 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.

2. Percentage of Participants Achieving Progression Free Survival (PFS) [Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.]

   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.

3. Objective Response Rate (ORR) [Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.]

   Objective response rate determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumours RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by RECIST at any post baseline visit. Per 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.

4. Duration of Response [Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.]

   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. Per 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.

5. Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline through approximately 30 days post treatment discontinuation; up to 6-months or to the data cutoff 11FEB2016.]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• An modified Glasgow Prognostic Score (mGPS) of 1 or 2 as defined below:

• Criteria:

1. mGPS of 1: C-reactive protein (CRP) > 10 mg/L and albumin ≥ 35 g/L

2. mGPS of 2: CRP > 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).

• Current or previous other malignancy within 2 years of study entry without sponsor approval

• Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency (DPD), or other known hypersensitivity to active substances, including fluorouracil (5-FU), ruxolitinib, or any of their excipients.

• Prior treatment with a JAK inhibitor for any indication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		Fayetteville	Arkansas	United States
3		Beverly Hills	California	United States
4		La Jolla	California	United States
5		Aurora	Colorado	United States
6		Denver	Colorado	United States
7		Washington	District of Columbia	United States
8		Fort Myers	Florida	United States
9		Saint Petersburg	Florida	United States
10		Athens	Georgia	United States
11		Atlanta	Georgia	United States
12		Macon	Georgia	United States
13		Thomasville	Georgia	United States
14		Harvey	Illinois	United States
15		Indianapolis	Indiana	United States
16		Kansas City	Kansas	United States
17		Louisville	Kentucky	United States
18		Baltimore	Maryland	United States
19		Boston	Massachusetts	United States
20		Farmington Hills	Michigan	United States
21		Kalamazoo	Michigan	United States
22		Lansing	Michigan	United States
23		Minneapolis	Minnesota	United States
24		Saint Louis Park	Minnesota	United States
25		Bolivar	Missouri	United States
26		Basking Ridge	New Jersey	United States
27		Cherry Hill	New Jersey	United States
28		Voorhees	New Jersey	United States
29		Commack	New York	United States
30		Fresh Meadows	New York	United States
31		Harrison	New York	United States
32		New York	New York	United States
33		Rochester	New York	United States
34		Rockville Centre	New York	United States
35		Sleepy Hollow	New York	United States
36		Canton	Ohio	United States
37		Cincinnati	Ohio	United States
38		Portland	Oregon	United States
39		Allentown	Pennsylvania	United States
40		Hershey	Pennsylvania	United States
41		Langhorne	Pennsylvania	United States
42		Greenville	South Carolina	United States
43		Chattanooga	Tennessee	United States
44		Knoxville	Tennessee	United States
45		Nashville	Tennessee	United States
46		Dallas	Texas	United States
47		Fort Worth	Texas	United States
48		Lubbock	Texas	United States
49		San Antonio	Texas	United States
50		Temple	Texas	United States
51		Salt Lake City	Utah	United States
52		Falls Church	Virginia	United States
53		Newport News	Virginia	United States
54		Seattle	Washington	United States
55		Green Bay	Wisconsin	United States
56		Graz		Austria
57		Linz		Austria
58		Salzburg		Austria
59		Vienna		Austria
60		Wein		Austria
61		Santiago		Chile
62		Vitacura		Chile
63		Bogota		Colombia
64		Medellin		Colombia
65		Naestved		Denmark
66		Odense C		Denmark
67		Bordeaux		France
68		Brest Cedex		France
69		Dijon		France
70		Lyon		France
71		Nancy		France
72		Cork		Ireland
73		Dubin		Ireland
74		Galway		Ireland
75		Beer Sheva		Israel
76		Haifa		Israel
77		Jerusalem		Israel
78		Petach Tikva		Israel
79		Ramat Gan		Israel
80		Tel Aviv		Israel
81		Tel Hashomer		Israel
82		Monterrey		Mexico
83		Oaxaca		Mexico
84		Toluca		Mexico
85		Amsterdam		Netherlands
86		Maastricht		Netherlands
87		Nijmegen		Netherlands
88		Braga		Portugal
89		Lisboa		Portugal
90		Porto		Portugal
91		San Juan		Puerto Rico
92		Linköping		Sweden
93		Uppsala		Sweden
94		Bellinzona		Switzerland
95		Geneve		Switzerland

Sponsors and Collaborators

• Incyte Corporation

Investigators

• Study Director: Fitzroy Dawkins, MD, Incyte Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT02119663
• Other Study ID Numbers: INCB 18424-363
• First Posted: Apr 22, 2014
• Last Update Posted: Feb 13, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Incyte Corporation: Metastatic pancreatic cancer
• Additional relevant MeSH terms: Pancreatic Neoplasms; Capecitabine

Study Results

Participant Flow

Recruitment Details	Participants with advanced or metastatic adenocarcinoma of the pancreas who had failed or were intolerant to first-line chemotherapy were randomized in the study.
Pre-assignment Detail	Treatment was started as soon as possible after randomization (within 3 days) and consisted of continuous 21-day cycles. Capecitabine was self-administered for the first 14 days of each cycle, and ruxolitinib/placebo was self-administered for the entire cycle.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Period Title: Overall Study
STARTED	43	43
COMPLETED	3	2
NOT COMPLETED	40	41

Baseline Characteristics

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine	Total
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Total of all reporting groups
Overall Participants	43	43	86
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.4 (10.63)	68.8 (8.43)	67.1 (9.68)
Age, Customized (Count of Participants)
≤ 65 years	20 46.5%	13 30.2%	33 38.4%
> 65 years	23 53.5%	30 69.8%	53 61.6%
Sex: Female, Male (Count of Participants)
Female	18 41.9%	21 48.8%	39 45.3%
Male	25 58.1%	22 51.2%	47 54.7%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival is reported here based on the number of deaths from randomization until the data cut-off.
Time Frame	Randomization until death due to any cause up to 6-months or to the data cutoff 11FEB2016.

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all participants randomized to the study.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	43	43
Observed deaths	29 67.4%	23 53.5%
Censored deaths	14 32.6%	20 46.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib Plus Capecitabine, Placebo Plus Capecitabine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.584
	Confidence Interval	(2-Sided) 95%; 0.886 to 2.830
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
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 as 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.
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 Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all participants randomized to the study.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	43	43
Median (95% Confidence Interval) [days]	48.0	61.0

3. Secondary Outcome

Title	Percentage of Participants Achieving Progression Free Survival (PFS)
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.
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 Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all participants randomized to the study.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	43	43
Survival rate at 3 months	0.337 0.8%	0.297 0.7%
Survival rate at 6 months	0.131 0.3%	0.204 0.5%

4. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumours RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by RECIST at any post baseline visit. Per 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.
Time Frame	Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all participants randomized to the study.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	43	43
Objective response	4.7 10.9%	2.3 5.3%
Complete response	2.3 5.3%	0.0 0%
Partial response	2.3 5.3%	2.3 5.3%

5. Secondary Outcome

Title	Duration of Response
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. Per 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.
Time Frame	Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population consisted of all participants randomized to the study.

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	43	43
Median (95% Confidence Interval) [days]	NA	NA

6. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAEs)
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).
Time Frame	Baseline through approximately 30 days post treatment discontinuation; up to 6-months or to the data cutoff 11FEB2016.

Outcome Measure Data

Analysis Population Description

The safety evaluable population consisted of all participants exposed to at least 1 dose of study drug (ruxolitinib or placebo).

Arm/Group Title	Ruxolitinib Plus Capecitabine	Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).	Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
Measure Participants	42	43
Participants who had any TEAEs	41 95.3%	40 93%
Participants who had treatment-related TEAEs	21 48.8%	25 58.1%
Participants who had SAEs	28 65.1%	20 46.5%
Participants who had Grade 3 or higher TEAEs	31 72.1%	31 72.1%
Participants hospitalized because of a TEAE	26 60.5%	18 41.9%
Participants discontinued treatment due to TEAE	7 16.3%	5 11.6%
Participants with a dose modification due to TEAE	17 39.5%	14 32.6%
Participants on concomitant medication due to TEAE	36 83.7%	35 81.4%
Participants with procedure performed due to TEAE	22 51.2%	14 32.6%
Participants who had a fatal TEAE	8 18.6%	2 4.7%

Adverse Events

Time Frame	From the first dose of study medication through the double-blind period through study termination up to 6-months or to the data cutoff 11FEB2016.
Adverse Event Reporting Description	The safety evaluable population consisted of all participants exposed to at least 1 dose of study drug (ruxolitinib or placebo).
Arm/Group Title	Ruxolitinib Plus Capecitabine		Placebo Plus Capecitabine
Arm/Group Description	Ruxolitinib 5 mg tablets in combination with Capecitabine 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).		Placebo 5 mg matching placebo tablets in combination with Capecitabine: 150 mg or 500 mg tablets to be administered by mouth twice daily (BID).
All Cause Mortality
	Ruxolitinib Plus Capecitabine		Placebo Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ruxolitinib Plus Capecitabine		Placebo Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/42 (66.7%)		20/43 (46.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/42 (2.4%)		0/43 (0%)
Cardiac disorders
Atrial fibrillation	0/42 (0%)		2/43 (4.7%)
Cardiac arrest	0/42 (0%)		1/43 (2.3%)
Cardiac failure	1/42 (2.4%)		0/43 (0%)
Gastrointestinal disorders
Abdominal pain	4/42 (9.5%)		2/43 (4.7%)
Ascites	2/42 (4.8%)		1/43 (2.3%)
Nausea	3/42 (7.1%)		4/43 (9.3%)
Small intestinal obstruction	3/42 (7.1%)		1/43 (2.3%)
Vomiting	1/42 (2.4%)		5/43 (11.6%)
Diarrhoea	1/42 (2.4%)		1/43 (2.3%)
Duodenal obstruction	1/42 (2.4%)		0/43 (0%)
Duodenal stenosis	0/42 (0%)		1/43 (2.3%)
Gastric stenosis	1/42 (2.4%)		0/43 (0%)
Gastrointestinal haemorrhage	0/42 (0%)		1/43 (2.3%)
Ileus	1/42 (2.4%)		0/43 (0%)
Stomatitis	0/42 (0%)		1/43 (2.3%)
General disorders
Pyrexia	1/42 (2.4%)		2/43 (4.7%)
Gait disturbance	0/42 (0%)		1/43 (2.3%)
General physical health deterioration	1/42 (2.4%)		0/43 (0%)
Sudden cardiac death	1/42 (2.4%)		0/43 (0%)
Sudden death	1/42 (2.4%)		0/43 (0%)
Hepatobiliary disorders
Cholangitis	2/42 (4.8%)		2/43 (4.7%)
Bile duct obstruction	1/42 (2.4%)		0/43 (0%)
Jaundice cholestatic	1/42 (2.4%)		0/43 (0%)
Portal vein thrombosis	0/42 (0%)		1/43 (2.3%)
Infections and infestations
Sepsis	2/42 (4.8%)		3/43 (7%)
Bacteraemia	1/42 (2.4%)		0/43 (0%)
Cellulitis	0/42 (0%)		1/43 (2.3%)
Peritonitis bacterial	0/42 (0%)		1/43 (2.3%)
Pneumonia	0/42 (0%)		1/43 (2.3%)
Injury, poisoning and procedural complications
Fall	1/42 (2.4%)		0/43 (0%)
Humerus fracture	1/42 (2.4%)		0/43 (0%)
Investigations
Blood bilirubin increased	1/42 (2.4%)		0/43 (0%)
Metabolism and nutrition disorders
Dehydration	3/42 (7.1%)		1/43 (2.3%)
Decreased appetite	1/42 (2.4%)		0/43 (0%)
Hyperkalaemia	0/42 (0%)		1/43 (2.3%)
Hypokalaemia	1/42 (2.4%)		1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/42 (2.4%)		1/43 (2.3%)
Musculoskeletal chest pain	0/42 (0%)		1/43 (2.3%)
Spinal pain	1/42 (2.4%)		0/43 (0%)
Nervous system disorders
Syncope	2/42 (4.8%)		0/43 (0%)
Cerebral ischaemia	0/42 (0%)		1/43 (2.3%)
Cognitive disorder	0/42 (0%)		1/43 (2.3%)
Headache	0/42 (0%)		1/43 (2.3%)
Hepatic encephalopathy	1/42 (2.4%)		0/43 (0%)
Psychiatric disorders
Confusional state	0/42 (0%)		1/43 (2.3%)
Renal and urinary disorders
Renal failure acute	0/42 (0%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/42 (9.5%)		1/43 (2.3%)
Pulmonary embolism	2/42 (4.8%)		2/43 (4.7%)
Skin and subcutaneous tissue disorders
Rash	0/42 (0%)		1/43 (2.3%)
Vascular disorders
Transient ischaemic attack	2/42 (4.8%)		0/43 (0%)
Deep vein thrombosis	1/42 (2.4%)		0/43 (0%)
Hypertension	0/42 (0%)		1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib Plus Capecitabine		Placebo Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/42 (90.5%)		40/43 (93%)
Blood and lymphatic system disorders
Anaemia	16/42 (38.1%)		10/43 (23.3%)
Leukocytosis	1/42 (2.4%)		3/43 (7%)
Gastrointestinal disorders
Abdominal pain	14/42 (33.3%)		4/43 (9.3%)
Nausea	11/42 (26.2%)		10/43 (23.3%)
Vomiting	10/42 (23.8%)		10/43 (23.3%)
Diarrhoea	10/42 (23.8%)		11/43 (25.6%)
Abdominal distension	10/42 (23.8%)		4/43 (9.3%)
Constipation	8/42 (19%)		11/43 (25.6%)
Ascites	5/42 (11.9%)		5/43 (11.6%)
Stomatitis	6/42 (14.3%)		3/43 (7%)
Abdominal pain upper	4/42 (9.5%)		4/43 (9.3%)
Flatulence	4/42 (9.5%)		1/43 (2.3%)
General disorders
Fatigue	9/42 (21.4%)		15/43 (34.9%)
Oedema peripheral	7/42 (16.7%)		8/43 (18.6%)
Pyrexia	6/42 (14.3%)		5/43 (11.6%)
Asthenia	7/42 (16.7%)		4/43 (9.3%)
Chills	3/42 (7.1%)		2/43 (4.7%)
Oedema	3/42 (7.1%)		2/43 (4.7%)
Chest pain	3/42 (7.1%)		0/43 (0%)
Malaise	0/42 (0%)		3/43 (7%)
Pain	0/42 (0%)		3/43 (7%)
Injury, poisoning and procedural complications
Fall	0/42 (0%)		4/43 (9.3%)
Investigations
Blood bilirubin increased	3/42 (7.1%)		3/43 (7%)
Weight decreased	3/42 (7.1%)		4/43 (9.3%)
Blood creatinine increased	0/42 (0%)		3/43 (7%)
Platelet count decreased	0/42 (0%)		3/43 (7%)
Metabolism and nutrition disorders
Decreased appetite	10/42 (23.8%)		12/43 (27.9%)
Hypokalaemia	7/42 (16.7%)		10/43 (23.3%)
Dehydration	5/42 (11.9%)		3/43 (7%)
Hyponatraemia	5/42 (11.9%)		2/43 (4.7%)
Hyperglycaemia	3/42 (7.1%)		6/43 (14%)
Hypoalbuminaemia	1/42 (2.4%)		5/43 (11.6%)
Hypophosphataemia	1/42 (2.4%)		3/43 (7%)
Musculoskeletal and connective tissue disorders
Back pain	4/42 (9.5%)		7/43 (16.3%)
Muscular weakness	0/42 (0%)		3/43 (7%)
Nervous system disorders
Dizziness	5/42 (11.9%)		3/43 (7%)
Psychiatric disorders
Anxiety	4/42 (9.5%)		1/43 (2.3%)
Depression	3/42 (7.1%)		1/43 (2.3%)
Insomnia	1/42 (2.4%)		3/43 (7%)
Renal and urinary disorders
Hematuria	3/42 (7.1%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/42 (9.5%)		2/43 (4.7%)
Cough	1/42 (2.4%)		3/43 (7%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	10/42 (23.8%)		10/43 (23.3%)
Skin hyperpigmentation	4/42 (9.5%)		0/43 (0%)
Dry skin	3/42 (7.1%)		1/43 (2.3%)
Rash	0/42 (0%)		3/43 (7%)
Vascular disorders
Hypertension	3/42 (7.1%)		0/43 (0%)
Hypotension	0/42 (0%)		4/43 (9.3%)

Limitations/Caveats

The study was terminated prior to the final analysis at the recommendation of the Data Monitoring Committee based on the review of efficacy in the 18424-362 (JANUS 1).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.