Clinical trial NCT02117479: Study of Ruxolitinib in Pancreatic Cancer Patients (Janus 1)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: Metastatic pancreatic cancer
Metastatic pancreatic adenocarcinoma that is recurrent
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2014-04-21
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Determining the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of advanced or metastatic pancreatic cancer.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization until death due to any cause; up to the data cutoff 11FEB2016.
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
measure: Percentage of Participants Achieving Progression Free Survival (PFS)
timeFrame: Randomization to disease progression, or death due to any cause if sooner; up to 6-months or to the data cutoff 11FEB2016.
measure: Objective Response Rate (ORR)
timeFrame: Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.
measure: Duration of Response
timeFrame: Baseline through end of study; up to 6-months or to the data cutoff 11FEB2016.
measure: Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline through approximately 30 days post treatment discontinuation; up to 6-months or to the data cutoff 11FEB2016.
Other outcomes:
Locations:
city: Avondale
country: United States
state: Arizona
city: Chandler
country: United States
state: Arizona
city: Gilbert
country: United States
state: Arizona
city: Glendale
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Surprise
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Jonesboro
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Bakersfield
country: United States
state: California
city: Berkeley
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Chula Vista
country: United States
state: California
city: Covina
country: United States
state: California
city: Downey
country: United States
state: California
city: El Cajon
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Gilroy
country: United States
state: California
city: Glendale
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lynwood
country: United States
state: California
city: Modesto
country: United States
state: California
city: Montebello
country: United States
state: California
city: Northridge
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Orange
country: United States
state: California
city: Redondo Beach
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Torrance
country: United States
state: California
city: Whittier
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Boulder
country: United States
state: Colorado
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Grand Junction
country: United States
state: Colorado
city: Longmont
country: United States
state: Colorado
city: Thornton
country: United States
state: Colorado
city: New Britain
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Southington
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Newark
country: United States
state: Delaware
city: Boca Raton
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Austell
country: United States
state: Georgia
city: Carrollton
country: United States
state: Georgia
city: Cartersville
country: United States
state: Georgia
city: Douglasville
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Newnan
country: United States
state: Georgia
city: Rome
country: United States
state: Georgia
city: Thomasville
country: United States
state: Georgia
city: Arlington Heights
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Hinsdale
country: United States
state: Illinois
city: Niles
country: United States
state: Illinois
city: Urbana
country: United States
state: Illinois
city: Goshen
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Topeka
country: United States
state: Kansas
city: Ashland
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Scarborough
country: United States
state: Maine
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Rockville
country: United States
state: Maryland
city: Worcester
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Woodbury
country: United States
state: Minnesota
city: Bolivar
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Kalispell
country: United States
state: Montana
city: Hastings
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Papillion
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Lebanon
country: United States
state: New Hampshire
city: East Orange
country: United States
state: New Jersey
city: Farmington
country: United States
state: New Mexico
city: Binghamton
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Fresh Meadows
country: United States
state: New York
city: Hudson
country: United States
state: New York
city: Johnson City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Nyack
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Wake Forest
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Middletown
country: United States
state: Ohio
city: Oregon
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Springfield
country: United States
state: Oregon
city: Tualatin
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Seneca
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Beaumont
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Cedar Park
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Denton
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Round Rock
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Blacksburg
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Roanoke
country: United States
state: Virginia
city: Salem
country: United States
state: Virginia
city: Wytheville
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Australian Capital Territory
country: Australia
city: New South Wales
country: Australia
city: South Australia
country: Australia
city: Victoria
country: Australia
city: Aalst
country: Belgium
city: Brugge
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Gilly
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Oshawa
country: Canada
state: Ontario
city: Sault Ste. Marie
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Laval
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Aschaffenburg
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Essen
country: Germany
city: Frankford
country: Germany
city: Koeln
country: Germany
city: Velbert
country: Germany
city: Aviano
country: Italy
city: Bari
country: Italy
city: Bergamo
country: Italy
city: Brescia
country: Italy
city: Cremona
country: Italy
city: Firenze
country: Italy
city: Genova
country: Italy
city: Lido di Camaiore
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Pisa
country: Italy
city: Rimini
country: Italy
city: Roma
country: Italy
city: Hwasun-gun
country: Korea, Republic of
city: Seongnam-si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
city: Badajoz
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Seville
country: Spain
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Patumwan
country: Thailand
city: Ratchathewi
country: Thailand
city: Seetatarom
country: Thailand
city: Aberdeen
country: United Kingdom
city: Bangor
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Boston
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Guildford
country: United Kingdom
city: Harlow
country: United Kingdom
city: Huddersfield
country: United Kingdom
city: Lancaster
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Southampton
country: United Kingdom
city: Sutton
country: United Kingdom
city: Welwyn Garden City
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Incyte Corporation
name: Fitzroy Dawkins, M.D.
role: STUDY_DIRECTOR
References:
citation: Hurwitz H, Van Cutsem E, Bendell J, Hidalgo M, Li CP, Salvo MG, Macarulla T, Sahai V, Sama A, Greeno E, Yu KH, Verslype C, Dawkins F, Walker C, Clark J, O'Reilly EM. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest New Drugs. 2018 Aug;36(4):683-695. doi: 10.1007/s10637-018-0580-2. Epub 2018 Mar 6.