An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
Condition: Advanced Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Tivozanib; Sorafenib
Intervention description: Tivozanib capsules, administered orally, on a dosing schedule of 3 weeks of treatment (beginning on Day 1) followed by 1 week off treatment. One cycle was defined as 4 weeks of treatment.; Sorafenib tablets, 400 mg twice daily, administered orally for 4 weeks (1 cycle = 4 weeks). One cycle was defined as 4 weeks of treatment. Cycles were repeated every 4 weeks.
Intervention MeSH terms: Sorafenib; Tivozanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 277.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Open-label, multi-center extension treatment protocol to allow access to tivozanib and
      sorafenib for subjects who have participated on the AV-951-09-301 protocol. Eligible subjects
      who were randomized to receive sorafenib on AV-951-09-301 and had documented progression of
      disease will receive a tivozanib dose of 1.5 mg/day. Eligible subjects who were randomized to
      tivozanib or sorafenib in AV-951-09-301, and displayed clinical benefit and acceptable
      tolerability to treatment, will continue to receive tivozanib or sorafenib at the same dose
      and schedule as in AV-951-09-301.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The subject must have participated on Protocol AV-951-09-301, and must meet either of
             the following bulleted criteria:

               -  Demonstrated disease progression per RECIST during treatment with sorafenib, OR

               -  Demonstrated clinical benefit [complete response (CR), partial response (PR), or
                  stable disease (SD) per RECIST] and acceptable tolerability after treatment with
                  tivozanib or sorafenib on protocol AV-951-09-301.

          2. Eastern Cooperative Oncology Group performance status ≤ 2 and life expectancy ≥ 3
             months.

          3. If female and of childbearing potential, documentation of negative pregnancy test
             prior to enrollment.

          4. Ability to give written informed consent

        Exclusion Criteria:

          1. Newly identified central nervous system (CNS) malignancies or documented progression
             of CNS metastases; subjects will be allowed only if the CNS metastases have been
             adequately treated with radiotherapy or surgery. For subjects receiving steroid
             therapy for allowed steroid maintenance therapy.

          2. Duration since last dose on Protocol AV-951-09-301:

               1. For subjects continuing tivozanib or sorafenib (subjects who demonstrated
                  clinical benefit and acceptable tolerability during treatment with tivozanib or
                  sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of
                  tivozanib or sorafenib.

               2. For subjects initiating tivozanib (ie demonstrated disease progression during
                  treatment with sorafenib): more than 4 weeks since last dose of sorafenib.
                  Subjects demonstrating disease progression due to CNS metastasis will be allowed
                  up to 8 weeks since last dose of sorafenib in order to complete treatment for CNS
                  metastasis.

          3. Inadequate recovery from any prior surgical procedure or major surgical procedure
             within 4 weeks prior to administration of first dose of study drug.

          4. Any of the following hematologic abnormalities:

               -  Hemoglobin < 9.0 g/dL

               -  Absolute neutrophil count < 1500 per mm3

               -  Platelet count < 75,000 per mm3

               -  Prothrombin time or Partial thromboplastin time >1.5 × upper limit of normal
                  (ULN)

          5. Any of the following serum chemistry abnormalities:

               -  Total bilirubin > 1.5 × ULN (or > 2.5 × ULN for subjects with Gilbert's syndrome)

               -  Aspartate aminotransferase or alanine aminotransferase > 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 > 2.0 × ULN

               -  Proteinuria > 3+ by urinalysis or urine dipstick

          6. If female, pregnant or lactating.

          7. 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 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).

          8. 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.

          9. Unhealed wounds (including active peptic ulcers).

         10. Serious/active infection or infection requiring parenteral antibiotics.

         11. Life-threatening illness or organ system dysfunction compromising safety evaluation.

         12. Psychiatric disorder, altered mental status precluding informed consent or necessary
             testing.

         13. Inability to comply with protocol requirements.

         14. Treatment with another anti-cancer therapy or participation in another interventional
             protocol (excluding AV-951-09-301).