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BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma

2022年7月7日 更新者：Hoosier Cancer Research Network

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

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.

研究概览

地位

完全的

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (实际的)

154

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 新加坡
      • Singapore、新加坡、169610
        • National Cancer Centre Singapore
  • 澳大利亚
    • New South Wales
      • Camperdown、New South Wales、澳大利亚、2050
        • Royal Prince Alfred Hospital: Sydney Cancer Centre
      • Randwick、New South Wales、澳大利亚、2031
        • Prince of Wales Hospital
      • Wahroonga、New South Wales、澳大利亚、2076
        • Sydney Adventist Hospital Ltd.
    • Queensland
      • Greenslopes、Queensland、澳大利亚、4120
        • Gallipoli Medical Research Foundation: Greenslopes Private Hospital
      • Herston、Queensland、澳大利亚、4029
        • Royal Brisbane & Women's Hospital
      • Woolloongabba、Queensland、澳大利亚、4201
        • Princess Alexandra Hospital
    • South Australia
      • Adelaide、South Australia、澳大利亚、5000
        • Royal Adelaide Hospital
      • Kurralta Park、South Australia、澳大利亚、5037
        • Ashford Cancer Centre
    • Tasmania
      • Launceston、Tasmania、澳大利亚、7250
        • Gallipoli Medical Research Foundation: Launceston General Hospital
    • Victoria
      • Frankston、Victoria、澳大利亚、3199
        • Peninsula Oncology Centre
      • Heidelberg、Victoria、澳大利亚、3084
        • Austin Hospital
      • Melbourne、Victoria、澳大利亚、3004
        • Alfred Hospital
    • Western Australia
      • Perth、Western Australia、澳大利亚、6000
        • Royal Perth Hospital
  • 美国
    • Alabama
      • Muscle Shoals、Alabama、美国、35661
        • Northwest Alabama Cancer Center
    • Arkansas
      • Hot Springs、Arkansas、美国、71913
        • Genesis Cancer Center
    • California
      • Burbank、California、美国、91505
        • Providence Health System: Roy and Patricia Disney Family Cancer Center
      • Corona、California、美国、92879
        • Compassionate Cancer Care Medical Group, Inc.
      • Corona、California、美国、92879
        • Compassionate Cancer Care Medical Group
      • Duarte、California、美国、91010
        • City of Hope
      • Fountain Valley、California、美国、92708
        • Robert A. Moss, M.D., FACP, Inc.
      • Fresno、California、美国、93720
        • California Cancer Associates for Research and Excellence
      • Greenbrae、California、美国、94904
        • Marin Specialty Care
      • Los Angeles、California、美国、90017
        • Good Samaritan Hospital
      • Los Angeles、California、美国、90095
        • UCLA Med - Hematology & Oncology
      • Riverside、California、美国、92501
        • Compassionate Cancer Care Medical Group
      • Whittier、California、美国、90603
        • American Institute of Research
    • Colorado
      • Denver、Colorado、美国、80210
        • Centura Health Research Center
      • Golden、Colorado、美国、80401
        • Western Oncology & Hematology
    • Florida
      • Brooksville、Florida、美国、34613
        • Cancer Care Centers of Florida: Brooksville
      • Fort Lauderdale、Florida、美国、33308
        • Broward Oncology Associates
      • Gainesville、Florida、美国、32610
        • University of Florida, Shands Cancer Center
      • Jacksonville、Florida、美国、32256
        • Cancer Specialists of North Florida
      • Miami、Florida、美国、33136
        • Advanced Pharma Cr, Llc
      • New Port Richey、Florida、美国、34652
        • Cancer Care Centers of Florida
      • Ocala、Florida、美国、34471
        • Ocala Cancer Institute
      • Rockledge、Florida、美国、32955
        • Cancer Care Centers of Brevard
    • Georgia
      • Athens、Georgia、美国、30607
        • Northeast Georgia Cancer Care, LLC
      • Dublin、Georgia、美国、31021
        • Dublin Hematology & Oncology Care
    • Idaho
      • Post Falls、Idaho、美国、83854
        • Kootenai Cancer Center
    • Illinois
      • Chicago、Illinois、美国、60611
        • Northwestern University, Robert H. Lurie Comprehensive Cancer Center
      • Galesburg、Illinois、美国、61401
        • Medical & Surgical Specialists, LLC
      • Skokie、Illinois、美国、60076
        • Edward H. Kaplan, M.D., & Associates
    • Indiana
      • Evansville、Indiana、美国、47713
        • Deaconess Clinic
      • Fort Wayne、Indiana、美国、46815
        • Fort Wayne Oncology & Hematology, Inc
      • Goshen、Indiana、美国、46527
        • IU Health Goshen
      • Indianapolis、Indiana、美国、46202
        • Indiana University Melvin and Bren Simon Cancer Center
      • Indianapolis、Indiana、美国、46219
        • IU Health Central Indiana Cancer Centers
      • Indianapolis、Indiana、美国、46256
        • Community Regional Cancer Center
      • Lafayette、Indiana、美国、47905
        • Horizon Oncology Research
      • Muncie、Indiana、美国、47303
        • IU Health at Ball Memorial Hospital Cancer Center
      • Munster、Indiana、美国、46321
        • Monroe Medical Associates
      • Newburgh、Indiana、美国、47630
        • Oncology Hematology Associates of SW Indiana
      • South Bend、Indiana、美国、46601
        • Northern Indiana Cancer Research Consortium
    • Iowa
      • Sioux City、Iowa、美国、51101
        • Siouxland Hematology Oncology Associates, LLP, Nylen Cancer Center
    • Kansas
      • Wichita、Kansas、美国、67214
        • Cancer Center of Kansas
    • Kentucky
      • Hazard、Kentucky、美国、41701
        • Kentucky Cancer Clinic
      • Paducah、Kentucky、美国、42001
        • Purchase Cancer Group
    • Louisiana
      • Baton Rouge、Louisiana、美国、70809
        • Medical Oncology LLC
      • Metairie、Louisiana、美国、70006
        • Metairie Oncologists
    • Massachusetts
      • Boston、Massachusetts、美国、02111
        • Tufts Medical Center
    • Michigan
      • Ann Arbor、Michigan、美国、48106
        • St. Joseph Mercy Hospital
      • Grand Rapids、Michigan、美国、49546
        • Cancer and Hematology Centers of Western Michigan
      • Wyoming、Michigan、美国、49519
        • Metro Health Cancer Care
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Mayo Clinic
    • Montana
      • Bozeman、Montana、美国、59715
        • Bozeman Deaconness Cancer Center
      • Great Falls、Montana、美国、59405
        • Sletten Cancer Specialists
    • Nebraska
      • Omaha、Nebraska、美国、68114
        • Methodist Cancer Center
    • New Hampshire
      • Manchester、New Hampshire、美国、03102
        • Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Elizabeth、New Jersey、美国、07202
        • Trinitas Regional Medical Center
      • Somerville、New Jersey、美国、08876
        • Somerset Hematology Oncology Associates
    • New Mexico
      • Albuquerque、New Mexico、美国、87110
        • Presbyterian Medical Group
      • Albuquerque、New Mexico、美国、87131
        • University of New Mexico Cancer Center: Albuquerque
    • New York
      • Albany、New York、美国、12208
        • New York Oncology Hematology, PC
      • Buffalo、New York、美国、14263
        • Roswell Park Cancer Institute
      • Lake Success、New York、美国、11042
        • NYU Langone Arena Oncology
      • New York、New York、美国、10029
        • Tisch Cancer Institute at Mount Sinai Medical Center
      • Nyack、New York、美国、10960
        • Hematology Oncology Associates of Rockland
    • North Carolina
      • Pinehurst、North Carolina、美国、28374
        • First Health of the Carolinas
    • Ohio
      • Middletown、Ohio、美国、45042
        • Signal Point Clinical Research Center
      • Wooster、Ohio、美国、44691
        • Lawrence M. Stallings, M.D.
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73120
        • Mercy Physicians Of Oklahoma
    • Oregon
      • Springfield、Oregon、美国、97477
        • Willamette Valley Cancer Institute
    • Pennsylvania
      • Danville、Pennsylvania、美国、17822
        • Geisinger Medical Center
      • Gettysburg、Pennsylvania、美国、17235
        • Gettysburg Cancer Center
      • Pittsburgh、Pennsylvania、美国、15212
        • Allegheny Cancer Center
      • State College、Pennsylvania、美国、16803
        • Mount Nittany Medical Center
      • West Reading、Pennsylvania、美国、19611
        • Berks Hematology Oncology Associates
    • Rhode Island
      • Cranston、Rhode Island、美国、02920
        • Hematology and Oncology Associates of Rhode Island
    • South Carolina
      • Charleston、South Carolina、美国、29425
        • MUSC Hollings Cancer Center
      • Hilton Head Island、South Carolina、美国、29926
        • South Carolina Cancer Specialists
    • Tennessee
      • Germantown、Tennessee、美国、38138
        • The Jones Clinic, PC
    • Texas
      • Austin、Texas、美国、78758
        • Texas Oncology: Austin North
      • Bedford、Texas、美国、76022
        • Texas Oncology: Bedford
      • Dallas、Texas、美国、75246
        • Texas Oncology, PA
      • Fort Worth、Texas、美国、76104
        • Texas Oncology: Fort Worth
      • Houston、Texas、美国、77030
        • Methodist Hospital Research Institute
      • Houston、Texas、美国、77024
        • Texas Oncology: Houston Memorial City
      • Houston、Texas、美国、77055
        • Houston Cancer Center
      • Lubbock、Texas、美国、79410
        • Joe Arrington Cancer Research and Treatment Center
      • San Antonio、Texas、美国、78229
        • CTRC at the UT Health Science Center at San Antonio
    • Virginia
      • Lynchburg、Virginia、美国、24501
        • Lynchburg Hematology Oncology Clinic, Inc.
    • Washington
      • Bremerton、Washington、美国、98310
        • Harrison HealthPartners Bremerton Hematology & Oncology
      • Kirkland、Washington、美国、98034
        • Cascade Cancer Center
      • Seattle、Washington、美国、98109
        • University of Washington, Seattle Cancer Care Alliance
      • Seattle、Washington、美国、98109
        • Group Health Medical Centers
      • Spokane、Washington、美国、99204
        • Rockwood Clinic
    • Wisconsin
      • Milwaukee、Wisconsin、美国、53226
        • University of Wisconsin, Clinical Cancer Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
药品：Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
药品：BNC105P
BNC105P, up to 16 mg/m^2
有源比较器：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.
药品：Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
药品：BNC105P
BNC105P, up to 16 mg/m^2

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
大体时间：Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Phase I
Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Phase I: Toxicities of BNC105P in Combination With Everolimus.
大体时间：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
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.
大体时间：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
6 months

次要结果测量

结果测量
措施说明
大体时间
Phase I: Response Rate of BNC105P in Combination With Everolimus.
大体时间：Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
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.
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.
大体时间：12 months
Determine the PK Profile for BN105P in combination with everolimus by calculating the geometric mean half-life of BNC105P
12 months
Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone
大体时间：12 months
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.
12 months
Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus.
大体时间：12 months
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
12 months
Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen.
大体时间：12 months
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.
12 months
Phase II: Overall Survival
大体时间：60 months
Determine overall survival probability, up to a maximum of 5 years from registration for protocol therapy.
60 months
Exploratory Objective: Correlation of PFS With Biomarkers
大体时间：6 months
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.
6 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Hoosier Cancer Research Network

合作者

Bionomics Limited

调查人员

  • 学习椅：Thomas Hutson, D.O.、Hoosier Cancer Research Network

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2010年1月1日

初级完成 (实际的)

2016年12月1日

研究完成 (实际的)

2016年12月1日

研究注册日期

首次提交

2009年12月15日

首先提交符合 QC 标准的

2009年12月15日

首次发布 (估计)

2009年12月17日

研究记录更新

最后更新发布 (实际的)

2022年7月11日

上次提交的符合 QC 标准的更新

2022年7月7日

最后验证

2017年4月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • HOG GU09-145

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