Clinical trial NCT01618370: Radium(223) Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases
Official title: Radium-223 Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Radium 223
Alpharadin
Prostate Cancer
Bone metastases
Castrate resistant prostate cancer
Hormone refractory prostate cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2012-06-13
Enrollment: 705
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a prospective, interventional, open-label, multi-center early access program for the use of Ra-223 Cl2 in HRPC/CRPC (Hormone refractory prostate cancer / Castrate resistant prostate cancer) patients diagnosed with bone metastasis and to collect additional short and long term safety data on the product.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years of age
* Histologically or cytologically confirmed prostate cancer
* Patients diagnosed with progressive bone predominant metastatic CRPC/HRPC (Hormone refractory prostate cancer / Castrate resistant prostate cancer) with at least 2 skeletal metastases on imaging with no lung, liver, and/or brain metastasis (lymph node only metastasis is allowed)
* Progressive disease is defined either by:

  * The appearance of new bone lesions. If progression is based on new lesion(s) on imaging only without an increase in prostate specific antigen (PSA), PSA values from 3 assessments within the last 6 months must be provided; OR
  * In the absence of new bone lesions by 2 subsequent increases in serum PSA over previous reference value, which should not be more than 6 months before screening, each measured at least 1 week apart with the last PSA ≥ 5 ng/mL. (The reference value time point 1, is defined as the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart. If the PSA at time point 3 is greater than the PSA at time point 2, then eligibility has been met. If the PSA at time point 3 is not greater than the PSA at time point 2 but the PSA value at time point 4 and/or time point 5 is greater than the PSA at time point 2, the patient is eligible assuming that other criteria are met)
* Life expectancy ≥ 6 months
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 - 2
* Adequate hematological, liver, and renal function

  * Absolute neutrophil count (ANC) ≥ 1.5 x10\^9/L
  * Platelet count ≥ 100 x10\^9/L
  * Hemoglobin ≥ 10.0 g/dL (100 g/L; 6.2 mmol/L)
  * Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  * Creatinine ≤ 1.5 x ULN
  * Albumin \> 25 g/L

Exclusion Criteria:

* Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period or follow-up
* Eligible for first course of docetaxel, i.e., patients who are fit enough, willing, and who are located where treatment with docetaxel is available
* Treatment with cytotoxic chemotherapy within previous 4 weeks, or failure to recover from AEs (adverse events) due to cytotoxic chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is permitted)
* Prior hemibody external radiotherapy is excluded. Patients who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets
* Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium-223 dichloride) for the treatment of bony metastases
* Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
* Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) (or other imaging modality based on institutional standard of care)
* Presence of brain metastases
* Lymphadenopathy exceeding 6 cm in short-axis diameter
* Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis
* Imminent or history of spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Patients with history of spinal cord compression should have completely recovered.
* Any other serious illness or medical condition, such as but not limited to:

  * Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2
  * Cardiac failure New York Heart Association (NYHA) III or IV
  * Crohn's disease or ulcerative colitis
  * Bone marrow dysplasia
* Fecal incontinence

Primary outcomes:
measure: Acute safety, variables will be summarized using descriptive statistics based on adverse events collection
timeFrame: From baseline to 30 days post-treatment
measure: Long-term safety, variables will be summarized using descriptive statistics based on adverse events collection
timeFrame: From 30 days post-treatment up to 3 years
Secondary outcomes:
measure: Brief Pain Inventory, as assessed by BPI-SF questionnaire (Brief Pain Inventory-Short Form)
timeFrame: From baseline up to 1 year
Other outcomes:
Locations:
city: Brugge
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Ottignies
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Plzen - Bory
country: Czech Republic
city: Praha 4
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Herlev
country: Denmark
city: København
country: Denmark
city: Odense
country: Denmark
city: Helsinki
country: Finland
city: HUS
country: Finland
city: Kuopio
country: Finland
city: Seinäjoki
country: Finland
city: Tampere
country: Finland
city: Angers Cedex 01
country: France
city: Avignon
country: France
city: Caen Cedex 5
country: France
city: Clermont Ferrand Cedex 1
country: France
city: Grenoble
country: France
city: La Roche Sur Yon Cedex
country: France
city: Lille Cedex
country: France
city: Lille
country: France
city: Montpellier Cedex
country: France
city: Montpellier
country: France
city: Paris Cedex 15
country: France
city: Paris
country: France
city: Paris
country: France
city: Poitiers Cedex
country: France
city: Saint Herblain
country: France
city: Suresnes
country: France
city: TOULOUSE cedex
country: France
city: Vandoeuvre les Nancy
country: France
city: Villejuif Cedex
country: France
city: Freiburg im Breisgrau
country: Germany
state: Baden-Württemberg
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Ulm
country: Germany
state: Baden-Württemberg
city: Erlangen
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state: Bayern
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Marburg
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Rostock
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state: Mecklenburg-Vorpommern
city: Rostock
country: Germany
state: Mecklenburg-Vorpommern
city: Braunschweig
country: Germany
state: Niedersachsen
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country: Germany
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state: Niedersachsen
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state: Nordrhein-Westfalen
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state: Nordrhein-Westfalen
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state: Nordrhein-Westfalen
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state: Nordrhein-Westfalen
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state: Sachsen
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state: Emilia-Romagna
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state: Emilia-Romagna
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city: Firenze
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Trento
country: Italy
state: Trentino-Alto Adige
city: Padova
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state: Veneto
city: Treviso
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state: Veneto
city: Verona
country: Italy
state: Veneto
city: Mexico, D.F.
country: Mexico
state: Distrito Federal
city: México
country: Mexico
state: Distrito Federal
city: Alkmaar
country: Netherlands
city: Amsterdam
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city: Bergen
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city: Bialystok
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city: Warszawa
country: Poland
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state: Barcelona
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state: Bilbao
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city: Palma de Mallorca
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state: Illes Baleares
city: Las Palmas de Gran Canaria
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state: Las Palmas
city: A Coruña
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city: Barcelona
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city: Barcelona
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city: Barcelona
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city: León
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city: Lugo
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city: Madrid
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city: Madrid
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city: Madrid
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city: Madrid
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city: Malaga
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city: Málaga
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city: Oviedo
country: Spain
city: Pamplona
country: Spain
city: Salamanca
country: Spain
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Eskilstuna
country: Sweden
city: Kalmar
country: Sweden
city: Karlstad
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Sundsvall
country: Sweden
city: Umeå
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Aarau
country: Switzerland
state: Aargau
city: Basel
country: Switzerland
state: Basel-Stadt
city: Chur
country: Switzerland
state: Graubünden
city: St. Gallen
country: Switzerland
state: Sankt Gallen
city: Bellinzona
country: Switzerland
state: Ticino
city: Lausanne
country: Switzerland
state: Vaud
city: Bern
country: Switzerland
city: Zürich
country: Switzerland
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Romford
country: United Kingdom
state: Essex
city: Leicester
country: United Kingdom
state: Leicestershire
city: Edinburgh
country: United Kingdom
state: Lothian
city: Bebington
country: United Kingdom
state: Merseyside
city: Northwood
country: United Kingdom
state: Middlesex
city: Nottingham
country: United Kingdom
state: Nottinghamshire
city: Taunton
country: United Kingdom
state: Somerset
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Guildford
country: United Kingdom
state: Surrey
city: Sutton
country: United Kingdom
state: Surrey
city: Coventry
country: United Kingdom
state: Warwickshire
city: Birmingham
country: United Kingdom
state: West Midlands
city: Wolverhampton
country: United Kingdom
state: West Midlands
city: Aberdeen
country: United Kingdom
city: Belfast
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Derby
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Hull
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Saad F, Gillessen S, Heinrich D, Keizman D, O'Sullivan JM, Nilsson S, Miller K, Wirth M, Reeves J, Seger M, Carles J, Heidenreich A. Disease Characteristics and Completion of Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Radium-223 in an International Early Access Program. Clin Genitourin Cancer. 2019 Oct;17(5):348-355.e5. doi: 10.1016/j.clgc.2019.05.012. Epub 2019 May 31.
citation: Heidenreich A, Gillessen S, Heinrich D, Keizman D, O'Sullivan JM, Carles J, Wirth M, Miller K, Reeves J, Seger M, Nilsson S, Saad F. Radium-223 in asymptomatic patients with castration-resistant prostate cancer and bone metastases treated in an international early access program. BMC Cancer. 2019 Jan 7;19(1):12. doi: 10.1186/s12885-018-5203-y.
citation: Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, Levy J, Miller K, Nilsson S, Petrenciuc O, Tucci M, Wirth M, Federhofer J, O'Sullivan JM; Radium-223 International Early Access Program Investigators. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016 Sep;17(9):1306-16. doi: 10.1016/S1470-2045(16)30173-5. Epub 2016 Jul 26.