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

7 juillet 2022 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

154

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
Médicament: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Médicament: BNC105P
BNC105P, up to 16 mg/m^2
Comparateur actif: 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.
Médicament: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Médicament: BNC105P
BNC105P, up to 16 mg/m^2

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
Délai: 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.
Délai: 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.
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Phase I: Response Rate of BNC105P in Combination With Everolimus.
Délai: 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.
Délai: 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
Délai: 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.
Délai: 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.
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hoosier Cancer Research Network

Collaborateurs

Bionomics Limited

Les enquêteurs

  • Chaise d'étude: Thomas Hutson, D.O., Hoosier Cancer Research Network

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2010

Achèvement primaire (Réel)

1 décembre 2016

Achèvement de l'étude (Réel)

1 décembre 2016

Dates d'inscription aux études

Première soumission

15 décembre 2009

Première soumission répondant aux critères de contrôle qualité

15 décembre 2009

Première publication (Estimation)

17 décembre 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

11 juillet 2022

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 juillet 2022

Dernière vérification

1 avril 2017

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • HOG GU09-145

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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