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Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy

23 ottobre 2017 aggiornato da: Radiation Therapy Oncology Group

A Phase III Randomized Study to Evaluate the Efficacy of Zometa® for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer

RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. It is not yet known whether zoledronate is more effective than calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

OBJECTIVES:

Primary

  • Compare the potential benefit of bisphosphonate therapy comprising zoledronate plus vitamin D and calcium supplement vs standard therapy with vitamin D and calcium supplement in the prevention of osteoporosis and associated bone fractures in patients with locally advanced nonmetastatic adenocarcinoma of the prostate undergoing radiotherapy and luteinizing hormone-releasing hormone (LHRH) agonist therapy.

Secondary

  • Evaluate the potential benefit of these regimens on quality of life in these patients.
  • Evaluate the potential benefit in bone mineral density over a period of 3 years for patients treated with these regimens.

OUTLINE: This is randomized multicenter study. Patients are stratified according to T score of the hip by dual x-ray absorptiometry (DXA) scan (< -1.0 but > -2.5 vs ≥ - 1.0) and planned duration of luteinizing hormone-releasing hormone (LHRH) agonist therapy (1-2½ years vs > 2½ years). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline and every 6 months during treatment.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

109

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 6V5
        • British Columbia Cancer Agency - Vancouver Island Centre
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Doctor H. Bliss Murphy Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Margaret and Charles Juravinski Cancer Centre
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Cancer Care Program at Thunder Bay Regional Health Sciences
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Maisonneuve-Rosemont Hospital
      • Quebec City, Quebec, Canada, G1R 2J6
        • Centre Hospitalier Universitaire de Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CHUS-Hopital Fleurimont
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre at Pasqua Hospital
  • Stati Uniti
    • California
      • Chico, California, Stati Uniti, 95926
        • Enloe Cancer Center at Enloe Medical Center
      • Los Angeles, California, Stati Uniti, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Pomona, California, Stati Uniti, 91767
        • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
      • Roseville, California, Stati Uniti, 95661
        • Radiation Oncology Center - Roseville
      • Sacramento, California, Stati Uniti, 95815
        • Radiological Associates of Sacramento Medical Group, Incorporated
    • Colorado
      • Colorado Springs, Colorado, Stati Uniti, 80933
        • Penrose Cancer Center at Penrose Hospital
      • Pueblo, Colorado, Stati Uniti, 81004
        • St. Mary - Corwin Regional Medical Center
    • Georgia
      • Gainesville, Georgia, Stati Uniti, 30501
        • Northeast Georgia Medical Center
    • Illinois
      • Alton, Illinois, Stati Uniti, 62002
        • Saint Anthony's Hospital at Saint Anthony's Health Center
      • Arlington Heights, Illinois, Stati Uniti, 60005
        • Northwest Community Hospital
      • Harvey, Illinois, Stati Uniti, 60426
        • Ingalls Cancer Care Center at Ingalls Memorial Hospital
      • Olympia Fields, Illinois, Stati Uniti, 60461
        • Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
      • Urbana, Illinois, Stati Uniti, 61801
        • CCOP - Carle Cancer Center
    • Indiana
      • Goshen, Indiana, Stati Uniti, 46526
        • Center for Cancer Care at Goshen General Hospital
      • Indianapolis, Indiana, Stati Uniti, 46202
        • Methodist Cancer Center at Methodist Hospital
    • Kentucky
      • Lexington, Kentucky, Stati Uniti, 40536-0093
        • Lucille P. Markey Cancer Center at University of Kentucky
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Baltimore, Maryland, Stati Uniti, 21229
        • St. Agnes Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, Stati Uniti, 48202
        • Josephine Ford Cancer Center at Henry Ford Hospital
      • Detroit, Michigan, Stati Uniti, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Kalamazoo, Michigan, Stati Uniti, 49007-3731
        • West Michigan Cancer Center
    • Minnesota
      • Saint Cloud, Minnesota, Stati Uniti, 56303
        • CentraCare Clinic - River Campus
      • Saint Cloud, Minnesota, Stati Uniti, 56303
        • Coborn Cancer Center
    • Missouri
      • Cape Girardeau, Missouri, Stati Uniti, 63701
        • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
      • Kansas City, Missouri, Stati Uniti, 64131
        • CCOP - Kansas City
      • Saint Louis, Missouri, Stati Uniti, 63141
        • CCOP - St. Louis-Cape Girardeau
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
      • Saint Louis, Missouri, Stati Uniti, 63141
        • David C. Pratt Cancer Center at St. John's Mercy
      • Springfield, Missouri, Stati Uniti, 65804
        • St. John's Regional Health Center
      • Springfield, Missouri, Stati Uniti, 65807
        • Hulston Cancer Center at Cox Medical Center South
    • Montana
      • Billings, Montana, Stati Uniti, 59101
        • CCOP - Montana Cancer Consortium
      • Billings, Montana, Stati Uniti, 59101
        • Northern Rockies Radiation Oncology Center
      • Great Falls, Montana, Stati Uniti, 59405
        • Great Falls Clinic - Main Facility
    • Nevada
      • Las Vegas, Nevada, Stati Uniti, 89102
        • University Medical Center of Southern Nevada
      • Las Vegas, Nevada, Stati Uniti, 89106
        • CCOP - Nevada Cancer Research Foundation
      • Reno, Nevada, Stati Uniti, 89502
        • Renown Institute for Cancer at Renown Regional Medical Center
    • New Hampshire
      • Keene, New Hampshire, Stati Uniti, 03431
        • Kingsbury Center for Cancer Care at Cheshire Medical Center
      • Lebanon, New Hampshire, Stati Uniti, 03756-0002
        • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Camden, New Jersey, Stati Uniti, 08103
        • Cancer Institute of New Jersey at Cooper University Hospital - Camden
      • Vineland, New Jersey, Stati Uniti, 08360
        • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
      • Voorhees, New Jersey, Stati Uniti, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • New York
      • Binghamton, New York, Stati Uniti, 13905
        • Lourdes Regional Cancer Center
      • Brooklyn, New York, Stati Uniti, 11209
        • Veterans Affairs Medical Center - Brooklyn
      • Buffalo, New York, Stati Uniti, 14263-0001
        • Roswell Park Cancer Institute
      • East Syracuse, New York, Stati Uniti, 13057
        • CCOP - Hematology-Oncology Associates of Central New York
    • North Carolina
      • Asheville, North Carolina, Stati Uniti, 28801
        • Mission Hospitals - Memorial Campus
      • Goldsboro, North Carolina, Stati Uniti, 27534
        • Wayne Radiation Oncology
      • Raleigh, North Carolina, Stati Uniti, 27607
        • Cancer Centers of North Carolina - Raleigh
      • Wilson, North Carolina, Stati Uniti, 27893
        • Wilmed Radiation Oncology Services
    • Ohio
      • Akron, Ohio, Stati Uniti, 44307
        • McDowell Cancer Center at Akron General Medical Center
      • Akron, Ohio, Stati Uniti, 44309-2090
        • Summa Center for Cancer Care at Akron City Hospital
      • Cincinnati, Ohio, Stati Uniti, 45267
        • Charles M. Barrett Cancer Center at University Hospital
      • Salem, Ohio, Stati Uniti, 44460
        • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
      • West Chester, Ohio, Stati Uniti, 45069
        • Precision Radiotherapy at University Pointe
      • Wooster, Ohio, Stati Uniti, 44691
        • Cancer Treatment Center
    • Pennsylvania
      • Abington, Pennsylvania, Stati Uniti, 19001
        • Rosenfeld Cancer Center at Abington Memorial Hospital
      • Bryn Mawr, Pennsylvania, Stati Uniti, 19010
        • Bryn Mawr Hospital
      • Gettysburg, Pennsylvania, Stati Uniti, 17325
        • Adams Cancer Center
      • Paoli, Pennsylvania, Stati Uniti, 19301-1792
        • Cancer Center of Paoli Memorial Hospital
      • Philadelphia, Pennsylvania, Stati Uniti, 19111-2497
        • Fox Chase Cancer Center - Philadelphia
      • Wynnewood, Pennsylvania, Stati Uniti, 19096
        • Lankenau Cancer Center at Lankenau Hospital
      • York, Pennsylvania, Stati Uniti, 17405
        • York Cancer Center at Apple Hill Medical Center
    • Tennessee
      • Kingsport, Tennessee, Stati Uniti, 37662
        • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
    • Utah
      • Murray, Utah, Stati Uniti, 84157
        • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
      • Ogden, Utah, Stati Uniti, 84403
        • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
      • Provo, Utah, Stati Uniti, 84604
        • Utah Valley Regional Medical Center - Provo
      • Saint George, Utah, Stati Uniti, 84770
        • Dixie Regional Medical Center - East Campus
      • Salt Lake City, Utah, Stati Uniti, 84143
        • LDS Hospital
    • Vermont
      • Saint Johnsbury, Vermont, Stati Uniti, 05819
        • Norris Cotton Cancer Center - North
    • Virginia
      • Norfolk, Virginia, Stati Uniti, 23507
        • Sentara Cancer Institute at Sentara Norfolk General Hospital
      • Portsmouth, Virginia, Stati Uniti, 23708-2197
        • Naval Medical Center - Portsmouth
    • Washington
      • Yakima, Washington, Stati Uniti, 98902
        • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Wisconsin
      • Appleton, Wisconsin, Stati Uniti, 54911
        • Theda Care Cancer Institute
      • Green Bay, Wisconsin, Stati Uniti, 54307-3508
        • St. Vincent Hospital Regional Cancer Center
      • Marinette, Wisconsin, Stati Uniti, 54143
        • Bay Area Cancer Care Center at Bay Area Medical Center
      • Menomonee Falls, Wisconsin, Stati Uniti, 53051
        • Community Memorial Hospital Cancer Care Center
      • Milwaukee, Wisconsin, Stati Uniti, 53226
        • Medical College of Wisconsin Cancer Center
      • Milwaukee, Wisconsin, Stati Uniti, 53295
        • Veterans Affairs Medical Center - Milwaukee
      • Milwaukee, Wisconsin, Stati Uniti, 53215
        • Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
      • West Allis, Wisconsin, Stati Uniti, 53227
        • West Allis Memorial Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Maschio

Descrizione

Eligibility criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 12 months of registration;

  • Any one of the following clinical stages:

    • T3 disease, any N stage, M0 with any Gleason score and any prostate-specific antigen (PSA); < T3 stage, any N stage, M0 with Gleason's score ≥ 8 and any PSA; < T3 stage, any N stage, M0 with Gleason's score 7 and PSA ≥ 15 nanograms/ml; < T3 stage, any N stage, M0 with Gleason score < 7 and PSA ≥ 20 nanograms/ml.
  • A negative bone scan for metastatic disease;
  • It is mandatory that the treating physician determine the planned duration of LHRH therapy prior to the site registering the patient (minimum 1 year of therapy); If patient is receiving pre-treatment LHRH therapy, it must have begun ≤ 6 months prior to registration. If pelvic radiation therapy (RT) has started, it must have begun ≤ 8 weeks prior to registration;
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup to be done within 16 weeks prior to registration:
  • History/physical examination;
  • Dental evaluation, including history of dental surgery (e.g., extraction or implant);
  • Bone scan;
  • T and L spine films;
  • DXA scan: To be eligible the patient must have a scan on Lunar, Hologic, or Norland equipment only and the T scores in both the L spine and total hip must be > negative 2.5;
  • Zubrod Performance Status 0-1 within 16 weeks prior to registration; (8/16/07)
  • Age ≥ 18;
  • Serum creatinine within 4 weeks prior to registration (8/16/07)
  • Corrected serum calcium ≥ 8.4 and ≤ 10.6 mg/dl within 8 weeks prior to registration; note: for patients with an albumin of 4.0, corrected calcium=measured calcium. The formula for corrected calcium if serum albumin value is above or below 4.0 is as follows: Corrected calcium (mg/dl) = (4 - [patient's albumin (g/dl)] x 0.8) + patient's measured calcium (mg/dl)
  • Patients who are sexually active must be willing/able to use medically acceptable forms of contraception, as the treatment involved in this study may be significantly teratogenic.
  • Patient agrees to refrain from using all products listed in Section 9.2, "Non-permitted Supportive Therapy";
  • Post-prostatectomy patients are eligible.
  • Patient must sign study specific informed consent prior to study entry.

Ineligibility criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; e.g., carcinoma in situ of the breast or oral cavity are permissible;
  • Patients with baseline T scores of ≤ -2.5 are excluded.
  • Patients with baseline calculated creatinine clearance < 30 mL/min (estimated by Cockcroft-Gault formula below) are excluded. creatinine clearance male = [(140 - age) x (wt in kg)] / [(serum creatinine) x (72)]
  • Prior bisphosphonate therapy;
  • Prior pelvic radiation (other than for current prostate cancer) or prior systemic radiotherapeutic agents, such as strontium or samarium;
  • Patients receiving systemic chemotherapy, steroids, growth hormones, or calcitonin;
  • Patients with a history of Paget's disease or with uncontrolled thyroid or parathyroid dysfunction or with other diseases that influence bone metabolism;
  • Known hypersensitivity to zoledronic acid or other bisphosphonates;
  • Active dental problems at study entry, including infection of the teeth or jawbone; dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw, exposed bone in the mouth, or slow healing after dental procedures;
  • Recent or planned

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Terapia di supporto
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Zoledronic Acid
Zoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Integratore alimentare: Calcium
A single dose of 500 mg of elemental calcium orally each day for 3 years.
Integratore alimentare: Zoledronic acid
Patients receive IV over 15 minutes once every 6 months for 3 years. The goal dose of zoledronic acid is 4 mg, but the selection of dose is determined based on calculated creatinine clearance at baseline.
Altri nomi:
  • Zometa
  • zoledronato
Radiazione: radiation therapy
Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.
Droga: LHRH
LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.
Integratore alimentare: Vitamin D
400 IU (10μg), orally each day for 3 years.
Comparatore attivo: Control
Vitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Integratore alimentare: Calcium
A single dose of 500 mg of elemental calcium orally each day for 3 years.
Radiazione: radiation therapy
Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.
Droga: LHRH
LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.
Integratore alimentare: Vitamin D
400 IU (10μg), orally each day for 3 years.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Freedom From Any Bone Fracture (FABF) Rate at Three Years
Lasso di tempo: From randomization to 3 years
The time of failure was measured from the date of randomization to the date of documented bone fractures, defined as any fracture of the bone. The three-year FABF rate will be estimated by the Kaplan-Meier method.
From randomization to 3 years

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percent Change in Bone Mineral Density at 3 Years
Lasso di tempo: Baseline, 3 years from start of treatment
Bone mineral density (BMD) was measured by DXA scan (Dual X-ray absorptiometry) for five locations: lumbar, right total hip, left total hip, right femoral neck, and left femoral neck. The percent change at 3 years was calculated for each location by the following formula: Percent Change BMD = (BMD_3 years - BMD_Baseline)/ BMD_Baseline * 100.
Baseline, 3 years from start of treatment
Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years
Lasso di tempo: Baseline, 3 years from start of treatment
The FACT-G is a validated, 27-item measure. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for the physical, social and functional subscales, and 0-24 for the emotional subscale. Certain items, identified on the FACT-G scoring guides, must be reversed before it is added by subtracting the response from 4. All subscale totals are added together to form the FACT-G total score. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicates better QOL.
Baseline, 3 years from start of treatment
Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival
Lasso di tempo: From pre-treatment to 3 years from start of treatment
The EQ-5D is a standardized instrument for measuring generic health status used to generate health utilities, used to derive quality adjusted survival. Quality adjusted survival is computed using the weighted sum of times in different health states added up to a total quality-adjusted survival time. The log-rank test is used to compare quality-adjusted survivals between the treatment arms.
From pre-treatment to 3 years from start of treatment

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Radiation Therapy Oncology Group

Collaboratori

National Cancer Institute (NCI)

Investigatori

  • Investigatore principale: Colleen A. Lawton, MD, Medical College of Wisconsin
  • Cattedra di studio: Matthew R. Smith, MD, Massachusetts General Hospital
  • Cattedra di studio: Margaret Chamberlain-Wilmoth, PhD, MSS, RN, Carolinas Medical Center - University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 marzo 2006

Completamento primario (Effettivo)

1 novembre 2014

Completamento dello studio (Effettivo)

1 novembre 2014

Date di iscrizione allo studio

Primo inviato

23 maggio 2006

Primo inviato che soddisfa i criteri di controllo qualità

23 maggio 2006

Primo Inserito (Stima)

25 maggio 2006

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

29 novembre 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

23 ottobre 2017

Ultimo verificato

1 ottobre 2017

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • RTOG 0518
  • CDR0000476469
  • NCI-2009-00884 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Condizioni

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Interventi farmacologici

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Sedi

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