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

Alok A Khorana, Saroj Vadhan-Raj, Nicole M Kuderer, Ted Wun, Howard Liebman, Gerald Soff, Chandra Belani, Eileen M O'Reilly, Robert McBane, John Eikelboom, C V Damaraju, Karen Beyers, Flavia Dietrich, Ajay K Kakkar, Hanno Riess, Renata D'Alpino Peixoto, Gary H Lyman, Alok A Khorana, Saroj Vadhan-Raj, Nicole M Kuderer, Ted Wun, Howard Liebman, Gerald Soff, Chandra Belani, Eileen M O'Reilly, Robert McBane, John Eikelboom, C V Damaraju, Karen Beyers, Flavia Dietrich, Ajay K Kakkar, Hanno Riess, Renata D'Alpino Peixoto, Gary H Lyman

Abstract

Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).

Keywords: anticoagulation risk stratification rivaroxaban venous thromboembolism neoplasms prophylaxis.

Conflict of interest statement

Conflict of Interests A.A.K. reports honoraria for co-chairing the steering committee for CASSINI from Janssen, and consulting fees from Bayer. S.V.-R. reports being a member of the Advisory Board for Janssen and has received compensation for consulting. N.M.K. reports being a research consultant for Janssen and Hospira, and reports spouse receiving research funds from Amgen. T.W. reports serving on Advisory Committees for CALLISTO and Janssen. H.L. reports serving as a consultant for Janssen Pharmaceuticals. G.S. has received funding for research by Janssen Pharmaceuticals. C.B. reports serving on the Steering Committee and as an Advisory Council member for the CASSINI trial—Johnson & Johnson. E.M.O. reports receiving consulting reimbursement from Janssen. R.M. reports receiving a research grant from Bristol-Myers Squibb. J.E. reports receiving grant and honoraria support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, Daiichi-Sankyo, Janssen and GlaxoSmithKline. C.V.D. is an employee of Janssen Research & Development, LLC. K.B. is an employee of Janssen Pharmaceuticals, LLC. F.D. reports serving as a consultant for Janssen Pharmaceuticals; study responsible physician for the CASSINI trial. A.K. reports receiving grants and/or honoraria support from Bayer, Daiichi-Sankyo, Boehringer Ingelheim, Sanofi and Janssen. H.R. reports research grant from Bayer and honoraria from Boehringer Ingelheim, Bayer, Pfizer, Daiichi-Sankyo and Leo Pharma. R.D.P. reports no conflicts of interest. G.H.L. reports no conflicts of interest.

Figures

Fig. 1
Fig. 1
CASSINI study design. ECOG, Eastern Cooperative Oncology Group.

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