Phase I/II Study of BNC105P in Combination with Everolimus or Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase

INTERVENTION: Arm A: Everolimus 10mg Daily, BNC105P 16mg/m2 infusion on Day 1 and Day 8 of a 21 day cycle (combination arm). Drugs used on Arm A are given simultaneously: everolimus by oral administration daily, BNC105P by IV administration (on days 1 and 8 of a repeating 21 day cycle). Arm B: This is a sequential Arm. Arm B subjects are administered Everolimus at 10mg per day by oral administration until disease progression or unacceptable toxicity is observed (then Everolimus is ceased). Once this occurs, patients have the option to enter BNC105P only portion of Arm B. BNC105P given by IV administration at 16mg/m2 (on days 1 and 8 of a repeating 21 day cycle). CONDITION: Clear cell renal cell carcinoma PRIMARY OUTCOME: Improvement in 6‐month progression free survival (PFS) with the addition of BNC105P to everolimus. ; Recist defined tumor assessment. Measurement from the start of the treatment until the criteria for disease progression is met (or death occurs), taking as reference the smallest measurements recorded since the treatment started. The time to progression, in patients with documented disease progression at their first disease evaluation, will be considered the time between initiation of therapy and the date of first documentation of disease progression. The percentage of patients whom have achieved Progression Free Survival (PFS) at 6 months will be calculated. SECONDARY OUTCOME: To determine PFS with BNC105P alone in patients progressing on everolimus. ; Recist defined tumor assessment. Measurement from the start of the treatment until the criteria for disease progression is met (or death occurs), taking as reference the smallest measurements recorded since the treatment started. The time to progression, in patients with documented disease progression at their first disease evaluation, will be considered the time between initiation of therapy and the date of first documentation of disease progression. To determine response rate with combination therapy compared to everolimus alone. ; The objective response rate is the proportion of all patients with confirmed Partial Response or Complete Response according to RECIST, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). To determine the overall survival, up to a maximum of 5 years from registration for protocol therapy. ; The overall survival time for each patient is the number of days from the day of first treatment to the earlier of (1) death (from any cause) and (2) the last date of patient contact. If the survival time does not correspond to the patient’s death then it is treated as censored. To evaluate the adverse events of the combination. Clinical assessments will in part be used to confirm adverse events. Adverse events will be categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) as listed by the National Cancer Institute of the USA. Adverse events summaries are provided with the consent documentation and protocol documentation. INCLUSION CRITERIA: Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent orobtained separately. Age > or equal to 18 years at the time of consent. Karnofsky Performance Score (KPS) > or equal to 70 within 7 days prior to registration for protocol therapy. Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. NOTE: Females are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation. ligation, or bilateral oophorectomy) or they are postmenopausal. Females must not