Study of Ruxolitinib in Pancreatic Cancer Patients (Janus 1)

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02117479
• Collaborator: (none)
• Enrollment: 321
• Locations: 230
• Arms: 2
• Actual Duration (Months): 33.1
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Determining the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of advanced or 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 310 participants with advanced or metastatic adenocarcinoma of the pancreas who have failed, or were intolerant to first-line chemotherapy, were to be randomized (1:1) to one of the following treatment groups:

• Treatment A (N = 155): Capecitabine + ruxolitinib

• Treatment B (N = 155): 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 daily for each cycle. Treatment for all participants continued as long as the regimen was tolerated, and the participant did not meet discontinuation criteria. Participants who discontinued study treatment before study termination were monitored for safety up to 30-35 days from the end of treatment. All participants were followed for survival until study termination or the safety follow-up visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 321 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 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)
• Actual Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Dec 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 and 500 mg tablets to be administered by mouth twice daily (BID)
Active Comparator: Placebo plus capecitabine	Drug: Placebo; 5 mg tablets to be administered by mouth twice daily (BID); Drug: Capecitabine; 150 and 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 the data cutoff 11FEB2016.]

   Overall survival is reported here based on the number of deaths from randomization up to 6-months or to the data cutoff 11FEB2016.

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.]

   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.

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 RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) at any post baseline visit. Per Response Evaluation Criteria In Solid Tumors Criteria (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.

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

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

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

2. mGPS of 2: C-reactive protein >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).

• Prior severe reaction to fluoropyrimidines, known dihydropyrimidine dehydrogenase deficiency (DPD), or other known hypersensitivity to active substances, including fluorouracil (5-FU), or 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		Avondale	Arizona	United States
2		Chandler	Arizona	United States
3		Gilbert	Arizona	United States
4		Glendale	Arizona	United States
5		Mesa	Arizona	United States
6		Phoenix	Arizona	United States
7		Scottsdale	Arizona	United States
8		Surprise	Arizona	United States
9		Tucson	Arizona	United States
10		Hot Springs	Arkansas	United States
11		Jonesboro	Arkansas	United States
12		Anaheim	California	United States
13		Bakersfield	California	United States
14		Berkeley	California	United States
15		Beverly Hills	California	United States
16		Chula Vista	California	United States
17		Covina	California	United States
18		Downey	California	United States
19		El Cajon	California	United States
20		Fullerton	California	United States
21		Gilroy	California	United States
22		Glendale	California	United States
23		La Mesa	California	United States
24		Long Beach	California	United States
25		Los Angeles	California	United States
26		Lynwood	California	United States
27		Modesto	California	United States
28		Montebello	California	United States
29		Northridge	California	United States
30		Oceanside	California	United States
31		Orange	California	United States
32		Redondo Beach	California	United States
33		San Diego	California	United States
34		San Francisco	California	United States
35		San Luis Obispo	California	United States
36		Santa Ana	California	United States
37		Santa Maria	California	United States
38		Santa Monica	California	United States
39		Torrance	California	United States
40		Whittier	California	United States
41		Aurora	Colorado	United States
42		Boulder	Colorado	United States
43		Colorado Springs	Colorado	United States
44		Denver	Colorado	United States
45		Grand Junction	Colorado	United States
46		Longmont	Colorado	United States
47		Thornton	Colorado	United States
48		New Britain	Connecticut	United States
49		New Haven	Connecticut	United States
50		Southington	Connecticut	United States
51		Trumbull	Connecticut	United States
52		Newark	Delaware	United States
53		Boca Raton	Florida	United States
54		Hollywood	Florida	United States
55		Miami	Florida	United States
56		Pembroke Pines	Florida	United States
57		Atlanta	Georgia	United States
58		Austell	Georgia	United States
59		Carrollton	Georgia	United States
60		Cartersville	Georgia	United States
61		Douglasville	Georgia	United States
62		Marietta	Georgia	United States
63		Newnan	Georgia	United States
64		Rome	Georgia	United States
65		Thomasville	Georgia	United States
66		Arlington Heights	Illinois	United States
67		Chicago	Illinois	United States
68		Hinsdale	Illinois	United States
69		Niles	Illinois	United States
70		Urbana	Illinois	United States
71		Goshen	Indiana	United States
72		Indianapolis	Indiana	United States
73		Topeka	Kansas	United States
74		Ashland	Kentucky	United States
75		Louisville	Kentucky	United States
76		Metairie	Louisiana	United States
77		New Orleans	Louisiana	United States
78		Scarborough	Maine	United States
79		Annapolis	Maryland	United States
80		Baltimore	Maryland	United States
81		Bethesda	Maryland	United States
82		Rockville	Maryland	United States
83		Worcester	Massachusetts	United States
84		Ann Arbor	Michigan	United States
85		Detroit	Michigan	United States
86		Kalamazoo	Michigan	United States
87		Lansing	Michigan	United States
88		Woodbury	Minnesota	United States
89		Bolivar	Missouri	United States
90		Kansas City	Missouri	United States
91		Saint Louis	Missouri	United States
92		Kalispell	Montana	United States
93		Hastings	Nebraska	United States
94		Omaha	Nebraska	United States
95		Papillion	Nebraska	United States
96		Las Vegas	Nevada	United States
97		Lebanon	New Hampshire	United States
98		East Orange	New Jersey	United States
99		Farmington	New Mexico	United States
100		Binghamton	New York	United States
101		Bronx	New York	United States
102		Fresh Meadows	New York	United States
103		Hudson	New York	United States
104		Johnson City	New York	United States
105		New York	New York	United States
106		Nyack	New York	United States
107		Rochester	New York	United States
108		Durham	North Carolina	United States
109		Wake Forest	North Carolina	United States
110		Winston-Salem	North Carolina	United States
111		Canton	Ohio	United States
112		Columbus	Ohio	United States
113		Middletown	Ohio	United States
114		Oregon	Ohio	United States
115		Toledo	Ohio	United States
116		Eugene	Oregon	United States
117		Portland	Oregon	United States
118		Springfield	Oregon	United States
119		Tualatin	Oregon	United States
120		Philadelphia	Pennsylvania	United States
121		Charleston	South Carolina	United States
122		Seneca	South Carolina	United States
123		Spartanburg	South Carolina	United States
124		Chattanooga	Tennessee	United States
125		Knoxville	Tennessee	United States
126		Memphis	Tennessee	United States
127		Nashville	Tennessee	United States
128		Arlington	Texas	United States
129		Austin	Texas	United States
130		Beaumont	Texas	United States
131		Bedford	Texas	United States
132		Cedar Park	Texas	United States
133		Dallas	Texas	United States
134		Denton	Texas	United States
135		El Paso	Texas	United States
136		Fort Worth	Texas	United States
137		Houston	Texas	United States
138		Plano	Texas	United States
139		Round Rock	Texas	United States
140		San Antonio	Texas	United States
141		Temple	Texas	United States
142		Tyler	Texas	United States
143		Waco	Texas	United States
144		Ogden	Utah	United States
145		Salt Lake City	Utah	United States
146		Blacksburg	Virginia	United States
147		Richmond	Virginia	United States
148		Roanoke	Virginia	United States
149		Salem	Virginia	United States
150		Wytheville	Virginia	United States
151		Seattle	Washington	United States
152		Vancouver	Washington	United States
153		Madison	Wisconsin	United States
154		Australian Capital Territory		Australia
155		New South Wales		Australia
156		South Australia		Australia
157		Victoria		Australia
158		Aalst		Belgium
159		Brugge		Belgium
160		Bruxelles		Belgium
161		Edegem		Belgium
162		Gent		Belgium
163		Gilly		Belgium
164		Kortrijk		Belgium
165		Leuven		Belgium
166		Calgary	Alberta	Canada
167		Oshawa	Ontario	Canada
168		Sault Ste. Marie	Ontario	Canada
169		Toronto	Ontario	Canada
170		Greenfield Park	Quebec	Canada
171		Laval	Quebec	Canada
172		Montreal	Quebec	Canada
173		Aschaffenburg		Germany
174		Berlin		Germany
175		Bochum		Germany
176		Essen		Germany
177		Frankford		Germany
178		Koeln		Germany
179		Velbert		Germany
180		Aviano		Italy
181		Bari		Italy
182		Bergamo		Italy
183		Brescia		Italy
184		Cremona		Italy
185		Firenze		Italy
186		Genova		Italy
187		Lido di Camaiore		Italy
188		Milano		Italy
189		Napoli		Italy
190		Pisa		Italy
191		Rimini		Italy
192		Roma		Italy
193		Hwasun-gun		Korea, Republic of
194		Seongnam-si		Korea, Republic of
195		Seoul		Korea, Republic of
196		Auckland		New Zealand
197		Christchurch		New Zealand
198		Hamilton		New Zealand
199		Badajoz		Spain
200		Barcelona		Spain
201		Madrid		Spain
202		Malaga		Spain
203		Seville		Spain
204		Taichung		Taiwan
205		Tainan		Taiwan
206		Taipei		Taiwan
207		Patumwan		Thailand
208		Ratchathewi		Thailand
209		Seetatarom		Thailand
210		Aberdeen		United Kingdom
211		Bangor		United Kingdom
212		Birmingham		United Kingdom
213		Boston		United Kingdom
214		Bristol		United Kingdom
215		Cardiff		United Kingdom
216		Glasgow		United Kingdom
217		Guildford		United Kingdom
218		Harlow		United Kingdom
219		Huddersfield		United Kingdom
220		Lancaster		United Kingdom
221		Leeds		United Kingdom
222		London		United Kingdom
223		Manchester		United Kingdom
224		Newcastle upon Tyne		United Kingdom
225		Nottingham		United Kingdom
226		Plymouth		United Kingdom
227		Southampton		United Kingdom
228		Sutton		United Kingdom
229		Welwyn Garden City		United Kingdom
230		Wirral		United Kingdom

Sponsors and Collaborators

• Incyte Corporation

Investigators

• Study Director: Fitzroy Dawkins, M.D., Incyte Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT02117479
• Other Study ID Numbers: INCB 18424-362
• First Posted: Apr 21, 2014
• Last Update Posted: Mar 26, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Incyte Corporation: Metastatic pancreatic cancer; Metastatic pancreatic adenocarcinoma that is recurrent
• 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	161	160
COMPLETED	5	4
NOT COMPLETED	156	156

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	161	160	321
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.3 (9.35)	65.6 (9.55)	66.4 (9.48)
Age, Customized (participants) [Number]
≤ 65 years	65 40.4%	68 42.5%	133 41.4%
> 65 years	96 59.6%	92 57.5%	188 58.6%
Sex: Female, Male (Count of Participants)
Female	66 41%	64 40%	130 40.5%
Male	95 59%	96 60%	191 59.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival is reported here based on the number of deaths from randomization up to 6-months or to the data cutoff 11FEB2016.
Time Frame	Randomization until death due to any cause; up 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	161	160
Observed	113 70.2%	124 77.5%
Censored	48 29.8%	36 22.5%

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	0.969
	Confidence Interval	(2-Sided) 95%; 0.747 to 1.256
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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	161	160
Median (95% Confidence Interval) [days]	43.0	44.0

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	1.056
	Confidence Interval	(2-Sided) 95%; 0.827 to 1.348
	Parameter Dispersion	Type: Value:
	Estimation Comments

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	161	160
Survival rate at 3 months	18.9 11.7%	19.8 12.4%
Survival rate at 6 months	6.1 3.8%	5.7 3.6%
Survival rate at 9 months	2.5 1.6%	3.4 2.1%
Survival rate at 12 months	2.5 1.6%	NA NaN

4. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment and was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria in Solid Tumours (RECIST) at any post baseline visit. Per Response Evaluation Criteria In Solid Tumors Criteria (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	161	160
Objective response	3.7 2.3%	1.9 1.2%
Complete response	0 0%	0 0%
Partial response	3.7 2.3%	1.9 1.2%

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.
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	161	160
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	153	154
Participants who had any TEAEs	152 94.4%	152 95%
Participants who had treatment-related TEAEs	73 45.3%	59 36.9%
Participants who had SAEs	94 58.4%	83 51.9%
Participants who had Grade 3 or higher TEAEs	112 69.6%	113 70.6%
Participants hospitalized because of a TEAE	89 55.3%	75 46.9%
Participants discontinued treatment due to TEAE	12 7.5%	22 13.8%
Participants with a dose modification due to TEAE	68 42.2%	48 30%
Participants on concomitant medication due to TEAE	131 81.4%	122 76.3%
Participants with procedure performed due to TEAE	60 37.3%	46 28.8%
Participants who had a fatal TEAE	20 12.4%	15 9.4%

Adverse Events

Time Frame	From the first dose of study medication 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	94/153 (61.4%)		83/154 (53.9%)
Blood and lymphatic system disorders
Anaemia	4/153 (2.6%)		3/154 (1.9%)
Disseminated intravascular coagulation	0/153 (0%)		1/154 (0.6%)
Febrile neutropenia	0/153 (0%)		2/154 (1.3%)
Leukocytosis	0/153 (0%)		1/154 (0.6%)
Neutropenia	0/153 (0%)		2/154 (1.3%)
Pancytopenia	0/153 (0%)		1/154 (0.6%)
Cardiac disorders
Acute myocardial infarction	1/153 (0.7%)		1/154 (0.6%)
Cardiac arrest	2/153 (1.3%)		0/154 (0%)
Cardiac failure	1/153 (0.7%)		0/154 (0%)
Coronary artery disease	1/153 (0.7%)		0/154 (0%)
Myocardial infarction	2/153 (1.3%)		1/154 (0.6%)
Sinus tachycardia	0/153 (0%)		1/154 (0.6%)
Tachycardia	0/153 (0%)		1/154 (0.6%)
Eye disorders
Conjunctival haemorrhage	1/153 (0.7%)		0/154 (0%)
Gastrointestinal disorders
Abdominal distension	0/153 (0%)		1/154 (0.6%)
Abdominal pain	6/153 (3.9%)		19/154 (12.3%)
Abdominal pain upper	0/153 (0%)		1/154 (0.6%)
Ascites	5/153 (3.3%)		1/154 (0.6%)
Colitis	1/153 (0.7%)		0/154 (0%)
Constipation	1/153 (0.7%)		4/154 (2.6%)
Diarrhoea	5/153 (3.3%)		4/154 (2.6%)
Duodenal obstruction	2/153 (1.3%)		3/154 (1.9%)
Duodenal stenosis	0/153 (0%)		1/154 (0.6%)
Dysphagia	1/153 (0.7%)		1/154 (0.6%)
Enteritis	1/153 (0.7%)		0/154 (0%)
Enterocolitis	1/153 (0.7%)		0/154 (0%)
Gastrointestinal haemorrhage	2/153 (1.3%)		1/154 (0.6%)
Haematemesis	1/153 (0.7%)		0/154 (0%)
Ileus	1/153 (0.7%)		0/154 (0%)
Impaired gastric emptying	1/153 (0.7%)		1/154 (0.6%)
Intestinal infarction	0/153 (0%)		1/154 (0.6%)
Intestinal obstruction	1/153 (0.7%)		2/154 (1.3%)
Intestinal perforation	1/153 (0.7%)		0/154 (0%)
Melaena	1/153 (0.7%)		1/154 (0.6%)
Nausea	4/153 (2.6%)		5/154 (3.2%)
Obstruction gastric	1/153 (0.7%)		0/154 (0%)
Oesophageal varices haemorrhage	1/153 (0.7%)		0/154 (0%)
Pancreatic pseudocyst	0/153 (0%)		1/154 (0.6%)
Peritoneal haemorrhage	0/153 (0%)		1/154 (0.6%)
Small intestinal obstruction	1/153 (0.7%)		2/154 (1.3%)
Stomatitis	2/153 (1.3%)		0/154 (0%)
Upper gastrointestinal haemorrhage	1/153 (0.7%)		3/154 (1.9%)
Vomiting	7/153 (4.6%)		4/154 (2.6%)
General disorders
Asthenia	0/153 (0%)		3/154 (1.9%)
Device leakage	0/153 (0%)		1/154 (0.6%)
Device malfunction	1/153 (0.7%)		0/154 (0%)
Fatigue	0/153 (0%)		1/154 (0.6%)
General physical health deterioration	0/153 (0%)		3/154 (1.9%)
Hypothermia	1/153 (0.7%)		0/154 (0%)
Malaise	0/153 (0%)		1/154 (0.6%)
Multi-organ failure	1/153 (0.7%)		0/154 (0%)
Oedema	0/153 (0%)		1/154 (0.6%)
Pain	3/153 (2%)		2/154 (1.3%)
Pyrexia	8/153 (5.2%)		1/154 (0.6%)
Systemic inflammatory response syndrome	0/153 (0%)		1/154 (0.6%)
Hepatobiliary disorders
Bile duct obstruction	1/153 (0.7%)		3/154 (1.9%)
Bile duct stenosis	1/153 (0.7%)		0/154 (0%)
Biliary dilatation	0/153 (0%)		1/154 (0.6%)
Biloma	0/153 (0%)		1/154 (0.6%)
Cholangitis	3/153 (2%)		2/154 (1.3%)
Cholecystitis acute	1/153 (0.7%)		0/154 (0%)
Cholelithiasis	0/153 (0%)		1/154 (0.6%)
Hepatic failure	1/153 (0.7%)		0/154 (0%)
Hepatic function abnormal	1/153 (0.7%)		0/154 (0%)
Hyperbilirubinaemia	0/153 (0%)		2/154 (1.3%)
Jaundice	3/153 (2%)		3/154 (1.9%)
Jaundice cholestatic	0/153 (0%)		1/154 (0.6%)
Portal vein thrombosis	0/153 (0%)		1/154 (0.6%)
Infections and infestations
Bacteraemia	0/153 (0%)		2/154 (1.3%)
Biliary sepsis	0/153 (0%)		2/154 (1.3%)
Biliary tract infection	2/153 (1.3%)		1/154 (0.6%)
Bronchitis	1/153 (0.7%)		0/154 (0%)
Candida infection	1/153 (0.7%)		0/154 (0%)
Cholangitis suppurative	1/153 (0.7%)		0/154 (0%)
Device related infection	1/153 (0.7%)		0/154 (0%)
Escherichia infection	1/153 (0.7%)		0/154 (0%)
Infection	2/153 (1.3%)		1/154 (0.6%)
Klebsiella infection	2/153 (1.3%)		0/154 (0%)
Klebsiella sepsis	1/153 (0.7%)		0/154 (0%)
Liver abscess	0/153 (0%)		1/154 (0.6%)
Lower respiratory tract infection	1/153 (0.7%)		0/154 (0%)
Peritonitis	1/153 (0.7%)		0/154 (0%)
Peritonitis bacterial	1/153 (0.7%)		0/154 (0%)
Pneumonia	4/153 (2.6%)		7/154 (4.5%)
Pneumonia klebsiella	0/153 (0%)		1/154 (0.6%)
Postoperative abscess	0/153 (0%)		1/154 (0.6%)
Sepsis	5/153 (3.3%)		5/154 (3.2%)
Septic shock	0/153 (0%)		2/154 (1.3%)
Skin candida	1/153 (0.7%)		0/154 (0%)
Urinary tract infection	2/153 (1.3%)		0/154 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/153 (0.7%)		0/154 (0%)
Fall	1/153 (0.7%)		0/154 (0%)
Spinal compression fracture	1/153 (0.7%)		0/154 (0%)
Investigations
Blood bilirubin increased	4/153 (2.6%)		1/154 (0.6%)
Hepatic enzyme increased	0/153 (0%)		1/154 (0.6%)
Liver function test abnormal	1/153 (0.7%)		0/154 (0%)
Platelet count decreased	1/153 (0.7%)		0/154 (0%)
Transaminases increased	1/153 (0.7%)		0/154 (0%)
White blood cell count decreased	1/153 (0.7%)		0/154 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/153 (0.7%)		1/154 (0.6%)
Dehydration	7/153 (4.6%)		4/154 (2.6%)
Failure to thrive	1/153 (0.7%)		2/154 (1.3%)
Hyperglycaemia	3/153 (2%)		2/154 (1.3%)
Hyperkalaemia	2/153 (1.3%)		0/154 (0%)
Hypoglycaemia	3/153 (2%)		1/154 (0.6%)
Hypokalaemia	2/153 (1.3%)		2/154 (1.3%)
Hyponatraemia	5/153 (3.3%)		1/154 (0.6%)
Hypovolaemia	0/153 (0%)		1/154 (0.6%)
Malnutrition	1/153 (0.7%)		1/154 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	1/153 (0.7%)		3/154 (1.9%)
Flank pain	0/153 (0%)		2/154 (1.3%)
Mobility decreased	0/153 (0%)		1/154 (0.6%)
Muscular weakness	1/153 (0.7%)		3/154 (1.9%)
Musculoskeletal pain	0/153 (0%)		1/154 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	2/153 (1.3%)		0/154 (0%)
Metastases to peritoneum	1/153 (0.7%)		0/154 (0%)
Small intestine carcinoma metastatic	1/153 (0.7%)		0/154 (0%)
Tumour associated fever	2/153 (1.3%)		0/154 (0%)
Tumour pain	1/153 (0.7%)		0/154 (0%)
Nervous system disorders
Complex regional pain syndrome	1/153 (0.7%)		0/154 (0%)
Dizziness	0/153 (0%)		1/154 (0.6%)
Encephalopathy	0/153 (0%)		1/154 (0.6%)
Headache	1/153 (0.7%)		0/154 (0%)
Ischaemic stroke	1/153 (0.7%)		0/154 (0%)
Lethargy	0/153 (0%)		1/154 (0.6%)
Parkinson's disease	1/153 (0.7%)		0/154 (0%)
Syncope	1/153 (0.7%)		1/154 (0.6%)
Unresponsive to stimuli	0/153 (0%)		1/154 (0.6%)
Psychiatric disorders
Confusional state	0/153 (0%)		1/154 (0.6%)
Delirium	2/153 (1.3%)		0/154 (0%)
Mental status changes	1/153 (0.7%)		0/154 (0%)
Anxiety	0/153 (0%)		1/154 (0.6%)
Renal and urinary disorders
Renal failure	3/153 (2%)		0/154 (0%)
Renal failure acute	5/153 (3.3%)		1/154 (0.6%)
Ureteric obstruction	1/153 (0.7%)		0/154 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/153 (0%)		1/154 (0.6%)
Chronic obstructive pulmonary disease	1/153 (0.7%)		0/154 (0%)
Cough	0/153 (0%)		1/154 (0.6%)
Dyspnoea	5/153 (3.3%)		4/154 (2.6%)
Epistaxis	1/153 (0.7%)		0/154 (0%)
Hypoxia	0/153 (0%)		1/154 (0.6%)
Pleural effusion	1/153 (0.7%)		5/154 (3.2%)
Pulmonary embolism	5/153 (3.3%)		2/154 (1.3%)
Pulmonary oedema	0/153 (0%)		1/154 (0.6%)
Respiratory arrest	1/153 (0.7%)		0/154 (0%)
Respiratory failure	1/153 (0.7%)		0/154 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/153 (0%)		1/154 (0.6%)
Vascular disorders
Embolism	1/153 (0.7%)		2/154 (1.3%)
Haematoma	1/153 (0.7%)		0/154 (0%)
Hypertension	0/153 (0%)		1/154 (0.6%)
Hypotension	3/153 (2%)		2/154 (1.3%)
Phlebitis	0/153 (0%)		1/154 (0.6%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib Plus Capecitabine		Placebo Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/153 (96.1%)		145/154 (94.2%)
Blood and lymphatic system disorders
Anemia	45/153 (29.4%)		22/154 (14.3%)
Gastrointestinal disorders
Nausea	45/153 (29.4%)		49/154 (31.8%)
Diarrhea	42/153 (27.5%)		36/154 (23.4%)
Abdominal pain	36/153 (23.5%)		49/154 (31.8%)
Vomiting	30/153 (19.6%)		46/154 (29.9%)
Constipation	33/153 (21.6%)		27/154 (17.5%)
Stomatitis	30/153 (19.6%)		18/154 (11.7%)
Ascites	21/153 (13.7%)		20/154 (13%)
Abdominal distension	15/153 (9.8%)		11/154 (7.1%)
Abdominal pain upper	13/153 (8.5%)		14/154 (9.1%)
Flatulence	9/153 (5.9%)		3/154 (1.9%)
Dry mouth	3/153 (2%)		8/154 (5.2%)
General disorders
Fatigue	47/153 (30.7%)		50/154 (32.5%)
Pyrexia	25/153 (16.3%)		13/154 (8.4%)
Oedema peripheral	18/153 (11.8%)		35/154 (22.7%)
Asthenia	17/153 (11.1%)		18/154 (11.7%)
Oedema	11/153 (7.2%)		3/154 (1.9%)
Chills	8/153 (5.2%)		4/154 (2.6%)
Infections and infestations
Urinary tract infection	9/153 (5.9%)		6/154 (3.9%)
Injury, poisoning and procedural complications
Fall	10/153 (6.5%)		4/154 (2.6%)
Investigations
Aspartate aminotransferase increased	10/153 (6.5%)		3/154 (1.9%)
Weight decreased	10/153 (6.5%)		6/154 (3.9%)
Alanine aminotransferase increased	9/153 (5.9%)		4/154 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	30/153 (19.6%)		47/154 (30.5%)
Dehydration	10/153 (6.5%)		9/154 (5.8%)
Hyponatraemia	9/153 (5.9%)		5/154 (3.2%)
Hyperglycaemia	4/153 (2.6%)		9/154 (5.8%)
Hypokalaemia	17/153 (11.1%)		12/154 (7.8%)
Musculoskeletal and connective tissue disorders
Back pain	19/153 (12.4%)		16/154 (10.4%)
Arthralgia	8/153 (5.2%)		4/154 (2.6%)
Muscular weakness	7/153 (4.6%)		5/154 (3.2%)
Pain in extremity	8/153 (5.2%)		2/154 (1.3%)
Nervous system disorders
Dizziness	19/153 (12.4%)		12/154 (7.8%)
Dysgeusia	4/153 (2.6%)		8/154 (5.2%)
Psychiatric disorders
Insomnia	13/153 (8.5%)		7/154 (4.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	9/153 (5.9%)		19/154 (12.3%)
Cough	10/153 (6.5%)		13/154 (8.4%)
Hiccups	9/153 (5.9%)		2/154 (1.3%)
Pleural effusion	8/153 (5.2%)		2/154 (1.3%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	37/153 (24.2%)		26/154 (16.9%)
Vascular disorders
Hypotension	12/153 (7.8%)		8/154 (5.2%)
Hypertension	8/153 (5.2%)		3/154 (1.9%)

Limitations/Caveats

The study was terminated as other related studies of ruxolitinib did not provide sufficient efficacy to warrant continuation at the recommendation of the Data Monitoring Committee.

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.