Clinical trial NCT02119663: A Study of Ruxolitinib in Pancreatic Cancer Patients
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: Metastatic pancreatic cancer
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2014-04-22
Enrollment: 86
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: This was to determine the efficacy, based upon overall survival, of ruxolitinib added to capecitabine for the treatment of metastatic pancreatic cancer.

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.

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
* 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization until death due to any cause up to 6-months or 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: Huntsville
country: United States
state: Alabama
city: Fayetteville
country: United States
state: Arkansas
city: Beverly Hills
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Fort Myers
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Athens
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Thomasville
country: United States
state: Georgia
city: Harvey
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Farmington Hills
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis Park
country: United States
state: Minnesota
city: Bolivar
country: United States
state: Missouri
city: Basking Ridge
country: United States
state: New Jersey
city: Cherry Hill
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Commack
country: United States
state: New York
city: Fresh Meadows
country: United States
state: New York
city: Harrison
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Rockville Centre
country: United States
state: New York
city: Sleepy Hollow
country: United States
state: New York
city: Canton
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Langhorne
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Falls Church
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Green Bay
country: United States
state: Wisconsin
city: Graz
country: Austria
city: Linz
country: Austria
city: Salzburg
country: Austria
city: Vienna
country: Austria
city: Wein
country: Austria
city: Santiago
country: Chile
city: Vitacura
country: Chile
city: Bogota
country: Colombia
city: Medellin
country: Colombia
city: Naestved
country: Denmark
city: Odense C
country: Denmark
city: Bordeaux
country: France
city: Brest Cedex
country: France
city: Dijon
country: France
city: Lyon
country: France
city: Nancy
country: France
city: Cork
country: Ireland
city: Dubin
country: Ireland
city: Galway
country: Ireland
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Monterrey
country: Mexico
city: Oaxaca
country: Mexico
city: Toluca
country: Mexico
city: Amsterdam
country: Netherlands
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Braga
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Linköping
country: Sweden
city: Uppsala
country: Sweden
city: Bellinzona
country: Switzerland
city: Geneve
country: Switzerland
Study officials:
affiliation: Incyte Corporation
name: Fitzroy Dawkins, MD
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.