A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism (VTE) Prophylaxis in Ambulatory Cancer Participants

NCT ID: NCT02555878

Last Updated: 2019-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 841 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-11
• Study Completion Date: 2018-08-24

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.

Conditions

Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Rivaroxaban

Participants will be administered rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

Rivaroxaban 10 milligram (mg) tablet will be administered orally once daily for 180 days.

Placebo

Participants will be administered matching placebo tablet orally once daily for 180 days.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo tablet will be administered orally once daily for 180 days.

Interventions

Rivaroxaban

Rivaroxaban 10 milligram (mg) tablet will be administered orally once daily for 180 days.

Intervention Type: DRUG

Placebo

Placebo tablet will be administered orally once daily for 180 days.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Phoenix, Arizona, United States

Tucson, Arizona, United States

Little Rock, Arkansas, United States

Los Angeles, California, United States

Martinez, California, United States

Santa Barbara, California, United States

Torrance, California, United States

Upland, California, United States

Denver, Colorado, United States

Norwich, Connecticut, United States

Gainesville, Florida, United States

Miami, Florida, United States

Miami Shores, Florida, United States

New Port Richey, Florida, United States

Atlanta, Georgia, United States

Evanston, Illinois, United States

Joliet, Illinois, United States

Peoria, Illinois, United States

Rockford, Illinois, United States

Skokie, Illinois, United States

Urbana, Illinois, United States

Anderson, Indiana, United States

Cedar Rapids, Iowa, United States

Brewer, Maine, United States

Baltimore, Maryland, United States

Silver Spring, Maryland, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

Rochester, Minnesota, United States

Saint Cloud, Minnesota, United States

Kansas City, Missouri, United States

Grand Island, Nebraska, United States

Las Vegas, Nevada, United States

Lebanon, New Hampshire, United States

Albany, New York, United States

East Syracuse, New York, United States

New York, New York, United States

Rochester, New York, United States

The Bronx, New York, United States

Charlotte, North Carolina, United States

High Point, North Carolina, United States

Cleveland, Ohio, United States

Eugene, Oregon, United States

Portland, Oregon, United States

Erie, Pennsylvania, United States

Charleston, South Carolina, United States

Greenville, South Carolina, United States

North Charleston, South Carolina, United States

Rapid City, South Dakota, United States

Nashville, Tennessee, United States

Abilene, Texas, United States

Austin, Texas, United States

Beaumont, Texas, United States

Bedford, Texas, United States

Dallas, Texas, United States

Denton, Texas, United States

Flower Mound, Texas, United States

Garland, Texas, United States

Houston, Texas, United States

Paris, Texas, United States

San Antonio, Texas, United States

Sugar Land, Texas, United States

Temple, Texas, United States

The Woodlands, Texas, United States

Tyler, Texas, United States

Waco, Texas, United States

Roanoke, Virginia, United States

Winchester, Virginia, United States

Green Bay, Wisconsin, United States

Weston, Wisconsin, United States

Amberloup, , Belgium

Bonheiden, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Laken (brussel), , Belgium

Turnhout, , Belgium

Wilrijk, , Belgium

Barretos, , Brazil

Caxias do Sul, , Brazil

Curitiba, , Brazil

Itajaí, , Brazil

Lajeado, , Brazil

Londrina, , Brazil

Mogi das Cruzes, , Brazil

Porto Alegre, , Brazil

Porto Alegre, Rs, , Brazil

Rio de Janeiro, , Brazil

Santo André, , Brazil

São José do Rio Preto, , Brazil

São Paulo, , Brazil

Sorocaba, , Brazil

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Toronto, Ontario, Canada

Saint-Jérôme, Quebec, Canada

Québec, , Canada

Benešov nad Černou, , Czechia

Brno, , Czechia

Jindřichův Hradec, , Czechia

Kladno, , Czechia

Liberec, , Czechia

Nový Jičín, , Czechia

Olomouc, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Tábor, , Czechia

Angers, , France

Avignon, , France

Dijon, , France

Hyers, , France

Le Mans, , France

Paris, , France

Rennes, , France

Saint-Herblain, , France

Valenciennes, , France

Berlin, , Germany

Brandenburg, , Germany

Cologne, , Germany

Dortmund, , Germany

Dresden, , Germany

Esslingen am Neckar, , Germany

Gauting, , Germany

Hamburg, , Germany

Hanover, , Germany

Herne, , Germany

Kiel, , Germany

Leipzig, , Germany

Lübeck, , Germany

Magdeburg, , Germany

Merseburg, , Germany

Minden, , Germany

München, , Germany

Paderborn, , Germany

Recklinghausen, , Germany

Weiden, , Germany

Arkhangelsk, , Russia

Chelyabinsk, , Russia

Kursk, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Omsk, , Russia

Saint Petersburg, , Russia

Tomsk, , Russia

Yaroslavi, , Russia

Bournemouth, , United Kingdom

Cheltenham, , United Kingdom

Dundee, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Plymouth, , United Kingdom

Swindon, , United Kingdom

Countries

United States; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Russia; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34807979 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33337539 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32663379 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30786186 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28933799 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

39039039STM4001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-001630-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107047

Identifier Type: -

Identifier Source: org_study_id