CompletedNCT03002220EXCAAPEUpdated Dec 11, 2024Results posted

Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status

A Phase 2 interventional study of radium-223 in Prostate Cancer, sponsored by MedSIR. Completed at 6 sites in Spain. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-11.

Sponsored by MedSIR · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 52
Allocation: Not applicable
Ages: 18 Years and older
Sex: Male

Study summary

Radium-223 is indicated for the treatment of patients with mCRPC with symptomatic bone metastases and no known visceral metastatic disease. However, very few data have been reported in patients with mCRPC who are asymptomatic or mildly symptomatic. Recently, results from an International Expanded Access Program have also suggested a benefit of radium-223 in asymptomatic patients with mCRPC. In addition, the mechanism of action of radium-223 should not be correlated with the presence/absence of the AR-V7 mutation, although this issue has not yet been evaluated.

The aim of this study is to assess the efficacy of radium-223 in asymptomatic patients with mCRPC, and to establish the association between AR-V7 status and radium-223 activity.

Read the detailed description

Primary objective:

To assess the efficacy of radium-223 in asymptomatic patients with mCRPC who have progressed while on abiraterone acetate or enzalutamide treatment.

Primary endpoint:

To determine the efficacy of radium-223 in terms of radiological rPFS.

Secondary objectives:

Safety profile.
To determine the association between AR-V7 status (positive vs. negative) and PFS.
To establish the relationship between CTCs number with radium-223 efficacy.

Secondary endpoints:

Safety AEs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) of the US National Cancer Institute (NCI) version 4.0 [20]. Grade 3 or 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the various combinations of drugs.

Efficacy

Radiographic progression-free survival (rPFS) depending on AR-V7 status.
Overall survival (OS).
Time to first symptomatic skeletal event (SSE).
Time to prostate specific antigen (PSA) progression according to the Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) study criteria.
Determination percentage of PSA progression.
Alkaline phosphatase level response (AF), normalization of alkaline phosphatase level, according to the ALSYMPCA study criteria.

Molecular aspects

Assessment of AR-V7 mutation evolution during the study treatment.
Determination changes in CTCs number during the study treatment.

Conditions studied

Prostate Cancer

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Prostatic Neoplasms 6,367

In context

Prostatic Neoplasms

6,367 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's enrollment of 52 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

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Lead sponsor

MedSIR is the lead sponsor of 55 studies on the registry; 11 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

Inclusion criteria

Subject is an adult ≥ 18 years at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
Subject has histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
Subject has bone metastases due to the prostate cancer and absence of visceral metastases.
Subject has a serum testosterone of ≤ 1.7 nmol/L (or ≤ 50 ng/dL) at screening.
Subject must have received a minimum of 24 weeks of treatment with abiraterone acetate or enzalutamide within its approved label indication and has discontinued use at least four weeks prior to start of study drug at day 1.
Prior use of docetaxel is allowed in castration-naïve patients (maximum of six cycles).
Subject receives and will continue to receive ongoing androgen deprivation with luteinising hormone-releasing hormone (LHRH) analogue therapy throughout the course of the study or has had a bilateral orchiectomy.
Subject is asymptomatic from prostate cancer, defined as patients with the score on brief pain inventory (short form) (BPI-SF) Question #3 must zero and no use of opiate analgesics for prostate cancer-related pain currently or anytime within two weeks prior to screening.
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at screening.
Subject receiving bisphosphonate or other approved bone-targeting therapy must have been on stable doses for at least four weeks prior to start of study drug at day 1.
Subject has a life expectancy of more than or equal to 12 months.
Subject agrees not to participate in another interventional study while on study drug.
Subject and his female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for six months after final study drug administration.

Exclusion criteria

Exclusion Criteria:

Subject has received any anti-neoplastic therapy (including ketoconazole and chemotherapy) following abiraterone acetate or enzalutamide discontinuation and prior to start of study drug at day 1.
Subject has known or suspected brain metastases or active leptomeningeal disease.
Subject has concurrent disease or any clinically significant abnormality following the investigator's review of the physical examination and safety laboratory tests at screening, which in the judgment of the investigator would interfere with the subject's participation in this study or evaluation of study results.
Subject has a history of another invasive cancer within three years prior to screening, with the exceptions of non-melanoma skin cancers or a non-infiltrating muscle bladder cancer that have a remote probability of recurrence in the opinion of the investigator in consultation with the medical monitor.
Subject had major surgery within one month prior to screening.
Subject has received investigational therapy within 28 days or 5 half lives, whichever is longer, prior to start of study drug at day 1.
Subject has absolute neutrophil count \< 1,500/μL, platelet count \< 100,000/μL, and hemoglobin \< 6.25 mmol/L (or \< 10 g/dL) at screening (Note: Subjects must not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at screening).
Subject has total bilirubin > 1.5 times the upper limit of normal (ULN) at screening, except for subjects with documented Gilbert's syndrome.
Subject has creatinine > 2.5 mg/dL at screening.
Subject has albumin ≤ 30 g/L (or ≤ 3.0 g/dL) at screening.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 52 participants (actual)

Study arms

Experimental
open-label
Patient will be treated with radium-223 at a dose of 55 kilobecquerel (kBq) (after 2015 National Institute of Standards and Technology's (NIST) implementation) per kilogram body weight, given at four-week intervals for six intravenous injections.
Drug: radium-223

Interventions

Drugradium-223
Radium-223 at a dose of 55 kBq
Also known as: Xofigo

What researchers measure

Primary outcomes

Assess the Efficacy of Radium-223 in Terms of Radiological rPFS
The primary efficacy endpoint is the median PFS (evaluated using RECIST v1.1) achieved with radium-223 treatment
Time frame: From date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months

Secondary outcomes

AEs and Serious Adverse Events (SAEs)
Time frame: Starting from the first procedure required by the study up to three months after study discontinuation.
Radiographic Progression-free Survival (rPFS) Depending on AR-V7 Status.
Time frame: From date of inclusion until Radiographic progression, assessed up to 20 months
Overall Survival (OS).
Time frame: From date of inclusion until death from any cause or the last date the patient was known to be alive, assessed up to 20 months.
Time to First Symptomatic Skeletal Event (SSE).
Time to first SSE defined as the time from treatment initiation until SSE (pathological fractures, vertebral or non-vertebral, spinal cord compression, radiation or surgery to bone). For all other events, the start date of the event/medication/therapy was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.
Time frame: From date of first drug administration until SSE, assessed up to 20 months
Time to PSA Progression According to the ALSYMPCA Study Criteria.
Time frame: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
PSA Progression
PSA progression (defined as PSA elevation ≥ 25% and ≥ 2 ng/mL after 12 weeks).
Time frame: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
Alkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level
Progression defined as FA elevation ≥ 25% after 12 weeks
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
Assessment of AR-V7 Mutation Evolution
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
Number of Participants With Change in CTCs Number
CTC levels will be measured at the start and at the end of the study. Patients will be categorized based on their CTC levels: those with a CTC count higher than 5, lower than 5, and CTC not reported. A lower CTC count is considered a better outcome.
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months

Results

Posted Dec 11, 2024

Limitations and caveats

For several endpoints, the upper confidence interval could not be calculated because either 50% of patients at the endpoint were not reached (in the case of DFS) or were reached very late in the study, close to EoS (such as rPFS, OS and PSA) and we could not meaningfully state the value of this data due to lack of information.

Participant flow

Between December 2016 (first patient in) and October 2018, 52 (82.5%) men from 63 patients with mCRPC with asymptomatic progression while on abiraterone acetate or enzalutamide were included in the study from 9 sites in Spain. In the protocol, the information stating that the trial would start in November was mostly an approximation. However, the trial ended up starting the following month.

Participant flow — Overall Study
Milestone	Open-label
Started	52
Completed	31
Not completed	21
Withdrew: Lack of efficacy	2
Withdrew: Withdrawal by subject	3
Withdrew: Adverse event	2
Withdrew: Disease progression	13
Withdrew: Physician decision	1

Outcome measures

PrimaryAssess the Efficacy of Radium-223 in Terms of Radiological rPFS

The primary efficacy endpoint is the median PFS (evaluated using RECIST v1.1) achieved with radium-223 treatment

Time frame:: From date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months
Reported as:: Median · months

Assess the Efficacy of Radium-223 in Terms of Radiological rPFS
months	Open-label
Assess the Efficacy of Radium-223 in Terms of Radiological rPFS	5.53 (5.3 to 5.6)

SecondaryAEs and Serious Adverse Events (SAEs)

Time frame:: Starting from the first procedure required by the study up to three months after study discontinuation.
Reported as:: Count of participants · Participants

AEs and Serious Adverse Events (SAEs)
Participants	Open-label
AEs and Serious Adverse Events (SAEs)	46

SecondaryRadiographic Progression-free Survival (rPFS) Depending on AR-V7 Status.

Time frame:: From date of inclusion until Radiographic progression, assessed up to 20 months
Reported as:: Median · months

Radiographic Progression-free Survival (rPFS) Depending on AR-V7 Status.
months	Open-label
AR-V7 negative	5.53 (5.3 to 5.53)
AR-V7 positive	2.2 (0.3 to NA)

SecondaryOverall Survival (OS).

Time frame:: From date of inclusion until death from any cause or the last date the patient was known to be alive, assessed up to 20 months.
Reported as:: Mean · months

Overall Survival (OS).
months	Open-label
Overall Survival (OS).	14.8 (11.2 to NA)

SecondaryTime to First Symptomatic Skeletal Event (SSE).

Time to first SSE defined as the time from treatment initiation until SSE (pathological fractures, vertebral or non-vertebral, spinal cord compression, radiation or surgery to bone). For all other events, the start date of the event/medication/therapy was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.

Time frame:: From date of first drug administration until SSE, assessed up to 20 months
Reported as:: Median · months

Time to First Symptomatic Skeletal Event (SSE).
months	Open-label
Time to First Symptomatic Skeletal Event (SSE).	NA (NA to NA)

SecondaryTime to PSA Progression According to the ALSYMPCA Study Criteria.

Time frame:: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
Reported as:: Median · months

Time to PSA Progression According to the ALSYMPCA Study Criteria.
months	Open-label
Time to PSA Progression According to the ALSYMPCA Study Criteria.	3.3 (1.9 to NA)

SecondaryPSA Progression

PSA progression (defined as PSA elevation ≥ 25% and ≥ 2 ng/mL after 12 weeks).

Time frame:: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months
Reported as:: Count of participants · Participants

PSA Progression
Participants	Open-label
PSA Progression	5

SecondaryAlkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level

Progression defined as FA elevation ≥ 25% after 12 weeks

Time frame:: From date of first study drug administration until End of Treatment, assessed up to 6 months
Reported as:: Count of participants · Participants

Alkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level
Participants	Open-label
Alkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level	17

SecondaryAssessment of AR-V7 Mutation Evolution

Time frame:: From date of first study drug administration until End of Treatment, assessed up to 6 months
Reported as:: Count of participants · Participants

Assessment of AR-V7 Mutation Evolution
Participants	Open-label
Baseline Evaluation — AR-V7 Negative	35
Baseline Evaluation — AR-V7 Positive	5
Baseline Evaluation — Not reported	12
EoT evaluation — AR-V7 Negative	26
EoT evaluation — AR-V7 Positive	1
EoT evaluation — Not reported	25

SecondaryNumber of Participants With Change in CTCs Number

CTC levels will be measured at the start and at the end of the study. Patients will be categorized based on their CTC levels: those with a CTC count higher than 5, lower than 5, and CTC not reported. A lower CTC count is considered a better outcome.

Time frame:: From date of first study drug administration until End of Treatment, assessed up to 6 months
Reported as:: Count of participants · Participants

Number of Participants With Change in CTCs Number
Participants	Open-label
Baseline Evaluation — CTC ≥ 5	10
Baseline Evaluation — CTC < 5	30
Baseline Evaluation — CTC Not reported	12
EoT Evaluation — CTC ≥ 5	4
EoT Evaluation — CTC < 5	24
EoT Evaluation — CTC Not reported	24

Adverse events

Collected over Baseline up to 2 years after last dose.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Open-label	3/52 (5.8%)	11/52 (21.2%)	30/52 (57.7%)

Most frequent serious events

Showing 10 of 13

Most frequent serious events
Event	Open-label
AnaemiaBlood and lymphatic system disorders	3/52
FeverGeneral disorders	2/52
FractureMusculoskeletal and connective tissue disorders	2/52
HematuriaRenal and urinary disorders	2/52
ThrombocytopeniaBlood and lymphatic system disorders	1/52
Acute kidney injuryRenal and urinary disorders	1/52
Congestive heart failureCardiac disorders	1/52
Flank painMusculoskeletal and connective tissue disorders	1/52
NauseaGastrointestinal disorders	1/52
Respiratory infectionRespiratory, thoracic and mediastinal disorders	1/52

Most frequent other events

Most frequent other events
Event	Open-label
AstheniaGeneral disorders	13/52
DiarrheaGastrointestinal disorders	4/52
NauseaGastrointestinal disorders	4/52
AnorexiaMetabolism and nutrition disorders	3/52
AthralgiaMusculoskeletal and connective tissue disorders	3/52
Bone painMusculoskeletal and connective tissue disorders	3/52

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Open-label
<=18 years	0
Between 18 and 65 years	0
>=65 years	52

Age, Continuous
Age, Continuous(years)	Open-label
Median	76.1 (69.4 to 82.3)

Sex: Female, Male
Sex: Female, Male(Participants)	Open-label
Female	0
Male	52

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Open-label
Hispanic or Latino	0
Not Hispanic or Latino	0
Unknown or Not Reported	52

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Open-label
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	0
More than one race	0
Unknown or Not Reported	52

Region of Enrollment
Region of Enrollment(participants)	Open-label
Spain	52

Study locations

6 sites

MedSIR Investigative site
Barcelona, Spain
MedSIR Investigative site
Cáceres, Spain
MedSIR Investigative site
Córdoba, Spain
MedSIR Investigative site
Lugo, Spain
MedSIR Investigative site
Madrid, Spain
MedSIR investigative site
Palma De Mallorca, 07120, Spain

References and documents

Publications

Carles J, Alonso-Gordoa T, Mellado B, Mendez-Vidal MJ, Vazquez S, Gonzalez-Del-Alba A, Piulats JM, Borrega P, Gallardo E, Morales-Barrera R, Paredes P, Reig O, Garcias de Espana C, Collado R, Bonfill T, Suarez C, Sampayo-Cordero M, Malfettone A, Garde J. Radium-223 for patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases progressing on first-line abiraterone acetate or enzalutamide: A single-arm phase II trial. Eur J Cancer. 2022 Sep;173:317-326. doi: 10.1016/j.ejca.2022.06.057. Epub 2022 Aug 16. PubMed 35981452 ↗

Study documents

Study protocol · Jan 30, 2020
Statistical analysis plan · Mar 12, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 11, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03002220
Lead sponsor: MedSIR
Collaborators: Bayer
Responsible party: Sponsor
First posted: Dec 23, 2016
Start date: Dec 21, 2016
Primary completion: May 6, 2020
Completion: Jun 9, 2021
Results posted: Dec 11, 2024
Last update: Dec 11, 2024

Study contacts

Joan Carles Galcerán

study director · H. Vall Hebrón

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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