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 Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 154
- 试验地点
- 107
- 主要终点
- Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological proof of component (any percent) of clear cell RCC (renal cell carcinoma).
- •Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory.
- •Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs).
- •Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy.
- •Written informed consent and HIPAA authorization for release of personal health information.
- •Age > 18 years at the time of consent.
- •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 4 weeks after treatment discontinuation.
- •Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy.
排除标准
- •No active brain metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration on protocol therapy. NOTE: A patient with prior brain metastasis are eligible if they have completed their radiation treatment for brain metastasis ≥30 days prior to registration for protocol therapy, are off steroids, and are asymptomatic.
- •No other currently active malignancy.
- •No treatment with any investigational agent within 14 days prior to registration for protocol therapy. NOTE: If treated with investigational agent within 14 days prior to registration, AE must be resolved back to baseline.
- •Prior cancer treatment must be completed at least 14 days prior to registration for protocol therapy and the patient must have recovered from the acute toxic effects of the regimen. With the exception of Bevacizumab treatment, which must be completed 30 days prior to registration for protocol therapy.
- •Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chart in the study procedure manual (SPM)] allowed if completed within 30 days prior to registration for protocol therapy.
- •Corrected QT interval (QTc) ≤ 450 msec at least 7 days prior to registration for protocol therapy.
- •No clinically significant infections as judged by the treating investigator.
- •No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
- •No collecting duct, medullary or sarcomatoid histology.
- •No prior treatment with temsirolimus or everolimus in the phase II component of the study. NOTE: Prior treatment with these agents is permitted in the phase I component of the study.
- •No use of full dose, therapeutic anti-coagulation with warfarin or related anti-coagulants or unfractionated or low molecular weight heparins.
- •No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1 anti-hypertensive medication).
- •No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of registration for protocol therapy.
- •No grade 2 or greater peripheral neuropathy.
研究组 & 干预措施
Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
干预措施: Everolimus (Drug)
Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
干预措施: BNC105P (Drug)
Sequential Arm B:Everolimus followed by BNC105P Monotherapy
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.
干预措施: Everolimus (Drug)
Sequential Arm B:Everolimus followed by BNC105P Monotherapy
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.
干预措施: BNC105P (Drug)
结局指标
主要结局
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
时间窗: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Phase I
Phase I: Toxicities of BNC105P in Combination With Everolimus.
时间窗: Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Determine the toxicities of BNC105P in combination with everolimus. Drug-related treatment emergent adverse events by CTCAE grade 2 or greater are reported
Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus.
时间窗: 6 months
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
次要结局
- Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.(12 months)
- Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus.(12 months)
- Phase I: Response Rate of BNC105P in Combination With Everolimus.(Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months)
- Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone(12 months)
- Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.(12 months)
- Phase II: Overall Survival(60 months)
- Exploratory Objective: Correlation of PFS With Biomarkers(6 months)