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

7. juli 2022 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

154

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Combination Arm A: Everolimus + BNC105P
Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle
Legemiddel: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Legemiddel: BNC105P
BNC105P, up to 16 mg/m^2
Aktiv komparator: 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.
Legemiddel: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals
Legemiddel: BNC105P
BNC105P, up to 16 mg/m^2

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Phase I: Response Rate of BNC105P in Combination With Everolimus.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Hoosier Cancer Research Network

Samarbeidspartnere

Bionomics Limited

Etterforskere

  • Studiestol: Thomas Hutson, D.O., Hoosier Cancer Research Network

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. januar 2010

Primær fullføring (Faktiske)

1. desember 2016

Studiet fullført (Faktiske)

1. desember 2016

Datoer for studieregistrering

Først innsendt

15. desember 2009

Først innsendt som oppfylte QC-kriteriene

15. desember 2009

Først lagt ut (Anslag)

17. desember 2009

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

11. juli 2022

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. juli 2022

Sist bekreftet

1. april 2017

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • HOG GU09-145

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