Clinical trial NCT02555878: A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism (VTE) Prophylaxis in Ambulatory Cancer Participants
Official title: Efficacy and Safety of Rivaroxaban Prophylaxis Compared With Placebo in Ambulatory Cancer Patients Initiating Systemic Cancer Therapy and at High Risk for Venous Thromboembolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neoplasms
Keywords: Cancer
Rivaroxaban
Venous thromboembolism
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2015-09-22
Enrollment: 841
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to demonstrate that rivaroxaban is superior to placebo for reducing the risk of the primary composite outcome as defined by objectively confirmed symptomatic lower extremity proximal deep vein thrombosis (DVT), asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal pulmonary embolism (PE), incidental PE, and venous thromboembolism (VTE)-related death in ambulatory adult participants with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE.

Detailed description: This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, superiority study comparing the efficacy and safety of rivaroxaban with placebo for primary prophylaxis of venous thromboembolism (VTE) in ambulatory adult participants, with various cancer types who are scheduled to initiate systemic cancer therapy. The study consists of 3 Phases: Screening Phase (14 Days), double-blind treatment Phase (180 Days) and follow up Phase (30 Days). The duration of participation in the study for each participant is approximately 32 weeks.

Eligibility criteria: Inclusion Criteria:

* Have histologically confirmed solid malignancy including but not limited to: pancreas, lung, stomach, colon, rectum, bladder, breast, ovary, renal or lymphoma (hematologic), with locally advanced or metastatic disease
* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Have a Khorana thromboembolic risk Score greater than or equal to (\>=) 2
* Creatinine clearance (CrCl) \>= 30 milliliter per minute (mL/min)
* Plan to initiate systemic cancer therapy within plus or minus (+-) 1 week of receiving the first dose of study drug with the intention of receiving systemic cancer therapy during the double-blind treatment period for an intended duration determined by the treating oncologist according to standard protocols of clinical care

Exclusion Criteria:

* Diagnosis of primary brain tumors
* Known history of brain metastases
* Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
* Hematologic malignancies with the exception of lymphoma
* Platelet count less than (\<) 50,000/millimeter\^3 (mm\^3), Life expectancy of less than or equal to (\<=) 6 months

Primary outcomes:
measure: Percentage of Participants With Time to First Occurrence of Primary Efficacy Endpoint (Composite and Components)
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to the First Occurrence of Major Bleeding Events as Defined by International Society of Thrombosis and Haemostasis (ISTH)
timeFrame: From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
Secondary outcomes:
measure: Percentage of Participants With Time to the First Occurrence of Symptomatic VTE Events or VTE-Related Deaths
timeFrame: Up to Day 180
measure: Percentage of Participants With All-Cause Mortality
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Arterial Thromboembolic Events (ATE)
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to the First Occurrence of Fatal or Non-fatal Visceral VTE
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to the First Occurrence of Composite Efficacy Endpoint 1
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 2
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 3
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to First Occurrence of Composite Efficacy Endpoint 4
timeFrame: Up to Day 180
measure: Percentage of Participants With Time to the First Occurrence of Clinically Relevant Non-major Bleeding
timeFrame: From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
measure: Percentage of Participants With Time to the First Occurrence of Minor Bleeding
timeFrame: From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
measure: Percentage of Participants With Time to the First Occurrence of Any Bleeding
timeFrame: From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Martinez
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Torrance
country: United States
state: California
city: Upland
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Norwich
country: United States
state: Connecticut
city: Gainesville
country: United States
state: Florida
city: Miami Shores
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Evanston
country: United States
state: Illinois
city: Joliet
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Rockford
country: United States
state: Illinois
city: Skokie
country: United States
state: Illinois
city: Urbana
country: United States
state: Illinois
city: Anderson
country: United States
state: Indiana
city: Cedar Rapids
country: United States
state: Iowa
city: Brewer
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Silver Spring
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Cloud
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Grand Island
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Lebanon
country: United States
state: New Hampshire
city: Albany
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: East Syracuse
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Erie
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: North Charleston
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Nashville
country: United States
state: Tennessee
city: Abilene
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: Dallas
country: United States
state: Texas
city: Denton
country: United States
state: Texas
city: Flower Mound
country: United States
state: Texas
city: Garland
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Paris
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: The Woodlands
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Roanoke
country: United States
state: Virginia
city: Winchester
country: United States
state: Virginia
city: Green Bay
country: United States
state: Wisconsin
city: Weston
country: United States
state: Wisconsin
city: Amberloup
country: Belgium
city: Bonheiden
country: Belgium
city: Brussel
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Laken (brussel)
country: Belgium
city: Turnhout
country: Belgium
city: Wilrijk
country: Belgium
city: Barretos
country: Brazil
city: Caxias do Sul
country: Brazil
city: Curitiba
country: Brazil
city: Itajai
country: Brazil
city: Lajeado
country: Brazil
city: Londrina
country: Brazil
city: Mogi das Cruzes
country: Brazil
city: Porto Alegre, Rs
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Santo André
country: Brazil
city: Sao Jose do Rio Preto
country: Brazil
city: Sao Paulo
country: Brazil
city: Sorocaba
country: Brazil
city: São Paulo
country: Brazil
city: Plovdiv N/a
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Toronto
country: Canada
state: Ontario
city: Saint-Jerome
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Benesov Nad Cernou
country: Czechia
city: Brno
country: Czechia
city: Jindrichuv Hradec
country: Czechia
city: Kladno
country: Czechia
city: Liberec
country: Czechia
city: Novy Jicin
country: Czechia
city: Olomouc
country: Czechia
city: Pardubice
country: Czechia
city: Praha 4
country: Czechia
city: Praha 5
country: Czechia
city: Tabor
country: Czechia
city: Angers Cedex 9
country: France
city: Angers
country: France
city: Avignon Cedex 9
country: France
city: Dijon Cedex
country: France
city: Hyers
country: France
city: Le Mans Cedex 2
country: France
city: Le Mans cedex 9
country: France
city: Paris
country: France
city: Rennes Cedex
country: France
city: Saint Herblain
country: France
city: Valenciennes
country: France
city: Berlin
country: Germany
city: Brandenburg
country: Germany
city: Dortmund
country: Germany
city: Dresden
country: Germany
city: Esslingen
country: Germany
city: Gauting
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Herne
country: Germany
city: Kiel
country: Germany
city: Koeln
country: Germany
city: Leipzig
country: Germany
city: Luebeck
country: Germany
city: Magdeburg
country: Germany
city: Merseburg
country: Germany
city: Minden
country: Germany
city: München
country: Germany
city: Paderborn
country: Germany
city: Recklinghausen
country: Germany
city: Weiden
country: Germany
city: Arkhangelsk
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Yaroslavi
country: Russian Federation
city: Bournemouth
country: United Kingdom
city: Cheltenham
country: United Kingdom
city: Dundee
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Swindon
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Khorana AA, Barnard J, Wun T, Vijapurkar U, Damaraju CV, Moore KT, Wildgoose P, McCrae KR. Biomarker signatures in cancer patients with and without venous thromboembolism events: a substudy of CASSINI. Blood Adv. 2022 Feb 22;6(4):1212-1221. doi: 10.1182/bloodadvances.2021005710.
citation: Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.
citation: Vadhan-Raj S, McNamara MG, Venerito M, Riess H, O'Reilly EM, Overman MJ, Zhou X, Vijapurkar U, Kaul S, Wildgoose P, Khorana AA. Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre-specified subgroup analysis of the randomized CASSINI study. Cancer Med. 2020 Sep;9(17):6196-6204. doi: 10.1002/cam4.3269. Epub 2020 Jul 14.
citation: Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. doi: 10.1056/NEJMoa1814630.
citation: Khorana AA, Vadhan-Raj S, Kuderer NM, Wun T, Liebman H, Soff G, Belani C, O'Reilly EM, McBane R, Eikelboom J, Damaraju CV, Beyers K, Dietrich F, Kakkar AK, Riess H, Peixoto RD, Lyman GH. Rivaroxaban for Preventing Venous Thromboembolism in High-Risk Ambulatory Patients with Cancer: Rationale and Design of the CASSINI Trial. Rationale and Design of the CASSINI Trial. Thromb Haemost. 2017 Nov 1;117(11):2135-2145. doi: 10.1160/TH17-03-0171. Epub 2017 Sep 21.