A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Tivozanib (AV-951); Placebo comparator
Intervention description: solid oral dosage form taken daily for three weeks per one month cycle; solid oral capsule containing excipients dosed daily for three weeks per month
Intervention MeSH terms: Tivozanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 272.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; AV-951; tivozanib

Summary:

      This phase 2 trial is evaluating the antineoplastic activity of tivozanib (AV-951) in
      treating patients with recurrent or metastatic renal cell cancer. Tivozanib (AV-951) is a
      VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking
      blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 18 year old males or females

          -  Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that
             is not amendable to surgical intervention

          -  Histologically or cytologically confirmed renal cell carcinoma

          -  Measurable disease

          -  No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC.

          -  No active brain metastases

          -  Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months

          -  No childbearing potential, or use of effective contraception during the study and for
             4 weeks after the last dose of study drug

          -  Archival paraffin embedded tumor tissue, if available.

          -  Ability to give written informed consent

        Exclusion Criteria:

          -  Pregnant or lactating women

          -  Primary CNS malignancies; active CNS metastases

          -  Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple
             myeloma)

          -  Any of the following hematologic abnormalities:

               -  Hemoglobin ≤ 9.0 g/dL

               -  ANC < 1500 per mm3

               -  Platelet count < 100,000 per mm3

          -  Any of the following serum chemistry abnormalities:

               -  Total bilirubin > 1.5 × the ULN

               -  AST or ALT ≥ 2.5 × the ULN

               -  Serum albumin < 3.0 g/dL

               -  Creatinine > 1.7 × ULN (or calculated CLCR <50 mL/min/1.73 m2)

               -  Proteinuria > 2.5 g/24 hours or 4+ with urine dipstick

          -  Significant cardiovascular disease, including:

               -  Active clinically symptomatic left ventricular failure

               -  Active HTN (diastolic blood pressure > 100 mmHg). Patients with a history of
                  hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4
                  weeks

               -  Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2
                  antihypertensive medications.

               -  Myocardial infarction within 3 months prior to administration of first study dose

          -  Unhealed wounds (including active gastric ulcers)

          -  Serious/active infection; infection requiring parenteral antibiotics

          -  Inadequate recovery from prior antineoplastic therapy

          -  Inadequate recovery from any prior surgical procedure; major surgical procedure within
             4 weeks prior to study entry

          -  Life-threatening illness or organ system dysfunction compromising safety evaluation

          -  Psychiatric disorder, altered mental status precluding informed consent or necessary
             testing

          -  Inability to comply with protocol requirements