The purpose of this study is to determine whether BNC105P in combination with/following everolimus is effective in the treatment of progressive metastatic clear cell renal cell carcinoma following prior tyrosine kinase inhibitors.
OUTLINE: This is a multi-center study. Phase I: Patients will be accrued in the classic 3 patients per dose per cohort design, 21-day cycle * Dose Level 1 Everolimus 10 mg BNC105P 4.2 mg/m2 * Dose Level 2 Everolimus 10 mg BNC105P 8.4 mg/m2 * Dose Level 3 Everolimus 10 mg BNC105P 12.6 mg/m2 * Dose Level 4 Everolimus 10 mg BNC105P 16 mg/m2 Phase II: Patients will be randomized 1:1 to Arm A or Arm B Combination Arm A: Everolimus 10 mg + BNC105P MTD (from Phase 1 study) 21 day cycle Sequential Arm B: Everolimus 10 mg 21 day cycle * Patients to receive BNC105P monotherapy at 16 mg/m2 following progression or intolerable toxicity on everolimus therapy. Karnofsky Performance Score (KPS) ≥70 within 7 days prior to registration for protocol therapy. Life Expectancy: Not specified Hematopoietic: * White blood cell count (WBC) \> 3.5 K/mm3 * Hemoglobin (Hgb) \> 8.5 g/dL * Platelets \> 100 K/mm3 * Absolute neutrophil count (ANC) \> 1.5 K/mm3 Hepatic: * Total Bilirubin \< 1.25 x ULN * Aminotransferase (AST and ALT) \< 2.5 x ULN Renal: * Serum Creatinine \< 2.5 x ULN (upper limit normal) Cardiovascular: * No significant cardiovascular events within 6 months (CVA, CAD, peripheral arterial obstruction, arrhythmias, cardiac dysfunction) of registration for protocol therapy * No history of clinical CHF or LVEF \<50% by Echo (or MUGA) within 30 days prior to registration for protocol therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
154
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
BNC105P, up to 16 mg/m\^2
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
Phase I
Time frame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Phase I: Toxicities of BNC105P in Combination With Everolimus.
Determine the toxicities of BNC105P in combination with everolimus. Drug-related treatment emergent adverse events by CTCAE grade 2 or greater are reported
Time frame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus.
Improvement in 6-month PFS with the addition of BNC105P to everolimus. Progression is defined using RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: 6 months
Phase I: Response Rate of BNC105P in Combination With Everolimus.
Number of objective responses per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.
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Northwest Alabama Cancer Center
Muscle Shoals, Alabama, United States
Genesis Cancer Center
Hot Springs, Arkansas, United States
Providence Health System: Roy and Patricia Disney Family Cancer Center
Burbank, California, United States
Compassionate Cancer Care Medical Group, Inc.
Corona, California, United States
Compassionate Cancer Care Medical Group
Corona, California, United States
City of Hope
Duarte, California, United States
Robert A. Moss, M.D., FACP, Inc.
Fountain Valley, California, United States
California Cancer Associates for Research and Excellence
Fresno, California, United States
Marin Specialty Care
Greenbrae, California, United States
Good Samaritan Hospital
Los Angeles, California, United States
...and 98 more locations
Determine the PK Profile for BN105P in combination with everolimus by calculating the geometric mean half-life of BNC105P
Time frame: 12 months
Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone
Objective response is defined as a confirmed CR or PR per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: 12 months
Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.
Median time to progression for arm P participants who crossed over to BNC105P monotherapy after progression. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: 12 months
Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.
Determine adverse events of everolimus and BNC105P when administered as a combination or sequential regimen. Total number of serious and non-serious adverse events for Arm A and Arm B are summarized. Complete adverse event information is supplied in the Adverse Events reporting section.
Time frame: 12 months
Phase II: Overall Survival
Determine overall survival probability, up to a maximum of 5 years from registration for protocol therapy.
Time frame: 60 months
Exploratory Objective: Correlation of PFS With Biomarkers
Exploratory analysis of serum biomarkers were undertaken to generate a potential signature for response. The correlation with 6 month progression free survival P value for four plasma biomarkers is reported.
Time frame: 6 months