Details

Details

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

IRB JAN1Y16

CC 16-694

Hospital Main Campus

Disease All Cancer Types

Drug Rivaroxaban Prophylaxis

Description

Description

Primary Objectives

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 DVT, asymptomatic lower extremity proximal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, and VTE-related death in ambulatory adult subjects with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE.

Secondary Objectives

To compare the efficacy of rivaroxaban with placebo for reducing the risk of symptomatic VTE events and VTE-related deaths, and all-cause mortality in ambulatory adult subjects with various cancer types receiving systemic cancer therapy who are at high risk of developing a VTE.

Safety Objectives

To assess the major bleeding events as defined by the International Society of Thrombosis and Hemostasis (ISTH).37 In addition, clinically relevant nonmajor bleeding, minor bleeding, and any bleeding (defined as major, clinically relevant non-major, and minor bleeding) will be assessed by ISTH definition.

Exploratory Objectives
  • To assess inflammation- and hypercoagulability-related biomarkers including d-dimer, p-selectin, and Tissue Factor
  • To analyze the steady state pharmacokinetics (PK) and exposure response of rivaroxaban
  • To collect health care resource utilization (HCRU) data that may be used in future economic modeling (the construction and reporting of the economic model will be conducted separately from this study)
Inclusion Criteria

Inclusion Criteria

  1. ≥18 years of age;
  2. 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;
  3. Have an ECOG Performance Status of 0-2 (see Attachment 4 , Functional Status Assessment Tool);
  4. Have a Khorana thromboembolic risk Score ≥2 (see Attachment 3, Cancer-Associated Venous Thromboembolism Risk Score);
  5. Have adequate renal function: CrCl ≥30 mL/min (see Attachment 2, Calculation of Creatinine Clearance using the Cockcroft-Gault formula);
  6. Plan to initiate systemic cancer therapy within +/-1 week of receiving the first dose of study drug with the intent of continuing systemic cancer therapy during the double-blind treatment period with study drug. Note: Subjects must either be 1) initiating their first systemic cancer therapy regimen based on initial diagnosis, 2) initiating their first cycle of a new systemic cancer therapy regimen for a recurrence, or 3) starting the first cycle of a new regimen of systemic cancer therapy based on tolerability or disease progression. Note: Every effort should be made to initiate systemic cancer therapy on the same day as the first dose of study drug or within 72 hours of the first dose of study drug when at all possible. However, subjects can continue in the study if there is a delay in initiation of systemic cancer therapy beyond +7 days after receiving the first dose of study drug.
  7. Be medically stable on the basis of physical examination, medical history, and vital signs performed at screening (or within 14 days before randomization on Day 1). If there are abnormalities, they must be consistent with the underlying illness in the study population.
  8. If a woman, before entry she must be: postmenopausal (for at least 12 months), or surgically sterile (have had a total hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or practicing a highly effective method of birth control, if sexually active, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method for less effective methods of contraception (eg, condoms, diaphragm, cervical cap, or sponge with spermicidal foam, cream, or gel), or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or not heterosexually active Note: subjects who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study.
  9. If a woman of childbearing potential, have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
  10. If a man, must agree to use adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 days after receiving the last dose of study drug.
  11. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol;
  12. Be able to provide informed consent and sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion Criteria

Exclusion Criteria

  1. Diagnosis of primary brain tumors
  2. Known history of brain metastases
  3. Bleeding diathesis, hemorrhagic lesions, active bleeding, and other conditions with a high risk for bleeding
  4. Hematologic malignancies with the exception of lymphoma
  5. Life expectancy of ≤6 months
  6. Significant comorbidities, that in the opinion of the treating physician would unnecessarily complicate participation in this clinical study, or provide excessive clinical risk to the subject to participate in this clinical study
  7. Diagnostically-confirmed significant liver disease or dysfunction. Examples of significant liver disease include acute clinical hepatitis, chronic active hepatitis, or cirrhosis; examples of significant liver dysfunction as defined by liver function test (LFT) abnormalities (confirmed by repeat-testing) include:
    • ALT >5x upper limit of normal (ULN)
    • ALT >3x ULN plus total bilirubin >2x ULN and a ratio of direct to total bilirubin ≥50%.
  8. Evidence of VTE on screening CU or incidental VTE identified on spiral CT scans ordered primarily for staging or restaging of malignancy ≤30 days prior to randomization
  9. Platelet count <50,000/mm3
  10. Activated partial thromboplastin time (aPTT) >1.5 ULN or International Normalized ration (INR) >1.5
  11. Subject has known allergies, hypersensitivity, or intolerance to rivaroxaban or its excipients (refer to IB)
  12. Concomitant use of anticoagulation therapy for prior VTE or other indications with either LMWH, warfarin, or direct oral anti-anticoagulants
  13. P2Y12 receptor antagonist anti-platelet therapy, daily non-steroidal anti-inflammatory drugs, or other medications known to increase the risk of bleeding (a daily dose of ≤100 mg of aspirin is permitted)
  14. Subject has any condition (ie atrial fibrillation) for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol specified assessments
  15. Combined P-glycoprotein (P-gp) and strong cytochrome P450 (CYP) 3A4 inhibitors (such as but not limited to ketoconazole, telithromycin or protease inhibitors) use within 4 days before randomization, or planned use during the study. Itraconazole use within 7 days before randomization or planned use during the study.
  16. Combined P-gp and strong CYP3A4 inducers (such as but not limited to rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort) use within 2 weeks before randomization, or planned use during the study.
  17. Inability to take oral medication
  18. Pregnant or breast-feeding or any plan to become pregnant during the study.
  19. Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.