Renal Clinical Trials

Cancer Clinical Trials

SLUHN 2016-22

A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Jillian Timer, RN, BSN
    484-503-4156

    Jillian.timer@sluhn.org
  • Treatment Agent: Tivozanib

    Synopsis: The purpose of this study is to compare the effectiveness of tivozanib in renal cell cancer compared to an approved drug “sorafenib” which works in a similar way to tivozanib. Tivozanib and sorafenib are both called “study medication”. This study will also see whether tivozanib is safe and tolerable for patients with advanced renal cell cancer.

     


    • 1. ≥ 18-years of age.

      2. Subjects with recurrent metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib. Postoperative or adjuvant systemic therapy will not be counted as a prior therapy unless recurrence is detected within 6 months of completion of treatment, in which case it will be counted as a prior therapy for metastatic disease.

      3. Subjects must have recovered from the adverse events of prior therapy or returned to baseline, and be off all therapy for at least 2 weeks.

      4. Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, mixed tumor containing predominantly sarcomatoid cells, and unclassified RCC are excluded).

      5. Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1.

      6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

      7. Life expectancy ≥ 3 months.

      8. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.

      9. Ability to give written informed consent and comply with protocol requirements.

      10. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for at least 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects and their partners must agree to use a highly effective method of contraception. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study) 
       
       

    • 1. Prior treatment with sorafenib or tivozanib.

      2. More than 3 prior regimens for metastatic RCC.

      3. Known central nervous system (CNS) diseases other than stable, treated brain metastases, defined as primary CNS malignancies or CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable by neuroimaging without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery). Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.

      4. Any of the following hematologic abnormalities:
      • Hemoglobin < 9.0 g/dL
      • Absolute neutrophil count (ANC) < 1500 per mm3
      • Platelet count < 100,000 per mm3

      5. Any of the following serum chemistry abnormalities:
      • Total bilirubin > 1.5 × upper limit of normal (ULN) (or > 2.5 × ULN for subjects with Gilbert’s syndrome)
      • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
      • Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone metastasis)
      • Creatinine > 1.5 × ULN unless creatinine clearance > 40 mL/min

      6. Significant cardiovascular disease, including:
      • Active clinically symptomatic left ventricular failure
      • Uncontrolled hypertension: Systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart
      • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug
      • History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation)
      • Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)

      7. Non-healing wound, bone fracture, or skin ulcer.

      8. Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.

      9. Serious/active infection or infection requiring parenteral antibiotics.

      10. Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.

      11. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
      • Symptomatic Pulmonary embolism
      • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
      • Peripheral arterial ischemia > Grade 2
      • Coronary or peripheral artery bypass graft

      12. Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:
      • Hematemesis, hematochezia, melena or other gastrointestinal bleeding ≥ Grade 2
      • Hemoptysis or other pulmonary bleeding ≥ Grade 2
      • Hematuria or other genitourinary bleeding ≥ Grade 2

      13. Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-muscle-invasive urothelial cancer, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.

      14. Pregnant or lactating females.

      15. History of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV), subjects on immune suppressive therapy for organ transplant.

      16. Life-threatening illness or organ system dysfunction compromising safety evaluation.

      17. Requirement for hemodialysis or peritoneal dialysis.

      18. Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely
      affects the absorption of tivozanib or sorafenib, major resection of the stomach or small bowel, or gastric bypass procedure.

      19. Psychiatric disorder or altered mental status precluding informed consent or necessary
      testing.

      20. Participation in another interventional protocol.