Clinical trial NCT01934790: Re-treatment Safety of Radium-223 Dichloride in Castration-resistant Prostate Cancer With Bone Metastases
Official title: A Re-treatment Safety Study of Radium-223 Dichloride in Subjects With Castration-resistant Prostate Cancer With Bone Metastases Who Received an Initial Course of Six Doses of Radium-223 Dichloride 50 kBq/kg Every Four Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-09-04
Enrollment: 45
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: Eligible subjects must have completed 6 doses of treatment of radium-223 dichloride and experienced no radium-223 dichloride-related SAEs (serious adverse events) or CTCAE (Common Terminology Criteria for Adverse Events) Grade 3 or 4 adverse event during or after the initial course of radium-223 dichloride that led to the discontinuation of treatment. 40 Subjects will be enrolled and will receive up to 6 doses of radium-223 dichloride 50 kBq/kg IV every 4 weeks.

The subject will be evaluated for AEs (adverse events) and laboratory tests at each visit every 4 weeks, prior to receiving radium-223 dichloride.

After the end of treatment visit the subjects will enter the active follow up period. Related AEs and SAEs and Lab tests will be evaluated at each visit every 4 weeks for the first 12 weeks, then every 12 weeks for up to 2 years after the last dose of radium-223 dichloride.

After the 2 years of active follow-up, subjects will enter the long-term follow-up period and will be followed via telephone follow-up at 6-month intervals for late toxicities and survival up to 7 years after the last dose of radium-223 dichloride or until death.

Joint safety reviews will regularly take place to oversee safety of the subjects conducted at regular intervals.

An interim analysis of the safety data will be conducted during the study.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate at any given point in time during disease history
* CRPC (castration-resistant prostate cancer) with clinical or radiologically confirmed bone progression
* Treatment with 6 injections of radium-223 dichloride 50 kBq/kg and no evidence of progression to bone (according to Prostate Cancer Clinical Trials Working Group 2 \[PCWG2\] criteria) during the first course of treatment
* Signed written informed consent prior to participating in any study related procedures. Willing and able to comply with the protocol, including follow-up visits and examinations

Exclusion Criteria:

* History of a radium-223 dichloride-related serious adverse event (SAE) or CTCAE Grade 3 or 4 adverse event (AE) during or after the initial course of radium-223 dichloride treatment that led to the discontinuation of treatment
* Less than 30 days from the last dose administered in the initial course of radium-223 dichloride treatment
* Visceral metastases 1 cm or greater in largest diameter and / or requiring local or systemic therapeutic intervention, as assessed by abdominal and pelvic magnetic resonance imaging (MRI) / computed tomography (CT) scan and / or chest X-ray within 30 days of the start of treatment
* Lymphadenopathy with lymph nodes exceeding 6 cm in short-axis diameter and / or requiring local or systemic therapeutic intervention. Enlarged lymph nodes of any size if the lymphadenopathy is thought to be a contributor to concurrent hydronephrosis.
* Current central nervous system (CNS) metastases
* Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
* Treatment with chemotherapy after the initial course of radium-223 dichloride treatment
* Prior hemibody external radiotherapy
* Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188
* Any other serious illness or medical conditions

  * Crohn's disease or ulcerative colitis
  * History of documented bone marrow dysplasia
  * Unmanageable fecal incontinence
* Imminent or established spinal cord compression based on clinical findings and / or MRI that has not yet been treated
* Other malignancy treated within the last 3 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: Up to 2.5 years
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Up to 2.5 years
measure: Number of Participants With Radium-223 Dichloride-related AEs in the Active Follow-up Period
timeFrame: Up to 2 years after last treatment
measure: Number of Participants With Radium-223 Dichloride-related SAEs in the Active Follow-up Period
timeFrame: Up to 2 years after last treatment
measure: Number of Participants With High/Low Abnormalities in Hematology Variables at Any Visit After Treatment Start
timeFrame: Up to 2.5 years
measure: Number of Participants With High/Low Abnormalities in Biochemistry Variables at Any Visit After Treatment Start
timeFrame: Up to 2.5 years
measure: Number of Participants Who Discontinued Radium-223 Dichloride Treatment Due to Treatment Emergent AEs or Death
timeFrame: Up to 2.5 years
Secondary outcomes:
Other outcomes:
measure: Radiological Progression Free Survival (rPFS)
timeFrame: Up to 2 years after last treatment
measure: Time to Radiological Bone Progression
timeFrame: Up to 2 years after last treatment
measure: Percentage of Participants With Total Alkaline Phosphatase (ALP) Response
timeFrame: Up to 2.5 years
measure: Time to Total ALP Progression
timeFrame: Up to 2 years after last treatment
measure: Percent Change in Total ALP
timeFrame: Baseline and Week 12, Week 24
measure: Percentage of Participants With Prostate Specific Antigen (PSA) Response
timeFrame: Up to 2.5 years
measure: Time to PSA Progression
timeFrame: Up to 2 years after last treatment
measure: Overall Survival
timeFrame: Up to 2 years after last treatment
measure: Percentage of Participants With Pain Improvement
timeFrame: Up to 2.5 years
measure: Time to Pain Progression
timeFrame: Up to 2.5 years
measure: Time to First Symptomatic Skeletal Event (SSE)
timeFrame: Up to 2 years after last treatment
measure: SSE-free Survival
timeFrame: Up to 2 years after last treatment
Locations:
city: New Orleans
country: United States
state: Louisiana
city: Omaha
country: United States
state: Nebraska
city: Syracuse
country: United States
state: New York
city: Kuopio
country: Finland
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petah Tikva
country: Israel
city: Forlì-Cesena
country: Italy
state: Emilia-Romagna
city: Milano
country: Italy
state: Lombardia
city: Bergen
country: Norway
city: Lørenskog
country: Norway
city: Córdoba
country: Spain
state: Andalucía
city: Barcelona
country: Spain
city: Málaga
country: Spain
city: Umeå
country: Sweden
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Sartor O, Heinrich D, Mariados N, Mendez Vidal MJ, Keizman D, Thellenberg Karlsson C, Peer A, Procopio G, Frank SJ, Pulkkanen K, Rosenbaum E, Severi S, Trigo J, Trandafir L, Wagner V, Li R, Nordquist LT. Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases. Prostate. 2019 Oct;79(14):1683-1691. doi: 10.1002/pros.23893. Epub 2019 Aug 23.