Trial Outcomes & Findings for Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status (NCT NCT03002220)

NCT ID: NCT03002220

Last Updated: 2024-12-11

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 52 participants
• Primary outcome timeframe: 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
• Results posted on: 2024-12-11

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.

Men ≥ 18 years. Signed ICF. mCRPC with bone metastases and asymptomatic progression. Serum testosterone levels ≤ 1.7 nmol/L at screening. Minimum of 24 weeks of treatment with abiraterone acetate or enzalutamide. Ongoing androgen deprivation with luteinizing releasing hormone (LHRH) analogue therapy or bilateral orchiectomy. ECOG score ≤ 1. Life expectancy ≥ 12w. Subject with female partner who is of childbearing potential must use two acceptable methods of birth control.

Participant milestones

Measure	Open-label Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Overall Study STARTED	52
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	21

Reasons for withdrawal

Measure	Open-label Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Overall Study Lack of Efficacy	2
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	2
Overall Study Disease progression	13
Overall Study Physician Decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	52 Participants n=5 Participants
Age, Continuous	76.1 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	52 Participants n=5 Participants
Region of Enrollment Spain	52 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Assess the Efficacy of Radium-223 in Terms of Radiological rPFS	5.53 months Interval 5.3 to 5.6

SECONDARY outcome

Timeframe: Starting from the first procedure required by the study up to three months after study discontinuation.

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
AEs and Serious Adverse Events (SAEs)	46 Participants

SECONDARY outcome

Timeframe: From date of inclusion until Radiographic progression, assessed up to 20 months

Population: There were an overall 40 patients with AR-V7 status known, 5 of them tested AR-V7 positive and 35 patients tested AR-V7 negative.

Outcome measures

Measure	Open-label n=40 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Radiographic Progression-free Survival (rPFS) Depending on AR-V7 Status. AR-V7 negative	5.53 months Interval 5.3 to 5.53
Radiographic Progression-free Survival (rPFS) Depending on AR-V7 Status. AR-V7 positive	2.2 months Interval 0.3 to There were insufficient events, or insufficient follow-up, to estimate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Overall Survival (OS).	14.8 months Interval 11.2 to Insufficient events or insufficient follow-up time, to estimate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: From date of first drug administration until SSE, assessed up to 20 months

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.

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Time to First Symptomatic Skeletal Event (SSE).	NA months The SSEs were reported in 5 patients (9.6%), therefore, the median time to first SSE was not reached

SECONDARY outcome

Timeframe: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Time to PSA Progression According to the ALSYMPCA Study Criteria.	3.3 months Interval 1.9 to Insufficient events or insufficient follow-up time, to estimate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: From date of first study drug administration to when PSA progression is observed, assessed up to 20 months

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

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
PSA Progression	5 Participants

SECONDARY outcome

Timeframe: From date of first study drug administration until End of Treatment, assessed up to 6 months

Progression defined as FA elevation ≥ 25% after 12 weeks

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Alkaline Phosphatase Level Response (AF), Normalization of Alkaline Phosphatase Level	17 Participants

SECONDARY outcome

Timeframe: From date of first study drug administration until End of Treatment, assessed up to 6 months

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Assessment of AR-V7 Mutation Evolution Baseline Evaluation · AR-V7 Negative	35 Participants
Assessment of AR-V7 Mutation Evolution Baseline Evaluation · AR-V7 Positive	5 Participants
Assessment of AR-V7 Mutation Evolution Baseline Evaluation · Not reported	12 Participants
Assessment of AR-V7 Mutation Evolution EoT evaluation · AR-V7 Negative	26 Participants
Assessment of AR-V7 Mutation Evolution EoT evaluation · AR-V7 Positive	1 Participants
Assessment of AR-V7 Mutation Evolution EoT evaluation · Not reported	25 Participants

SECONDARY outcome

Timeframe: From date of first study drug administration until End of Treatment, assessed up to 6 months

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.

Outcome measures

Measure	Open-label n=52 Participants Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Number of Participants With Change in CTCs Number Baseline Evaluation · CTC ≥ 5	10 Participants
Number of Participants With Change in CTCs Number Baseline Evaluation · CTC < 5	30 Participants
Number of Participants With Change in CTCs Number Baseline Evaluation · CTC Not reported	12 Participants
Number of Participants With Change in CTCs Number EoT Evaluation · CTC ≥ 5	4 Participants
Number of Participants With Change in CTCs Number EoT Evaluation · CTC < 5	24 Participants
Number of Participants With Change in CTCs Number EoT Evaluation · CTC Not reported	24 Participants

Adverse Events

Open-label

Serious events: 11 serious events

Other events: 30 other events

Deaths: 3 deaths

Serious adverse events

Measure	Open-label n=52 participants at risk Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
Blood and lymphatic system disorders Anaemia	5.8% 3/52 • Number of events 3 • Baseline up to 2 years after last dose.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
General disorders Fever	3.8% 2/52 • Number of events 2 • Baseline up to 2 years after last dose.
Musculoskeletal and connective tissue disorders Fracture	3.8% 2/52 • Number of events 2 • Baseline up to 2 years after last dose.
Renal and urinary disorders Hematuria	3.8% 2/52 • Number of events 2 • Baseline up to 2 years after last dose.
Renal and urinary disorders Acute kidney injury	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
Cardiac disorders Congestive heart failure	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
Musculoskeletal and connective tissue disorders Flank pain	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
Gastrointestinal disorders Nausea	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
Respiratory, thoracic and mediastinal disorders Respiratory infection	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
General disorders Uncontrolled pain	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
Gastrointestinal disorders Vomiting	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.
General disorders Worsening general condition	1.9% 1/52 • Number of events 1 • Baseline up to 2 years after last dose.

Other adverse events

Measure	Open-label n=52 participants at risk Patient will be treated with radium-223 at a dose of 55 kBq (after 2015 NIST implementation) per kilogram body weight, given at four-week intervals for six intravenous injections. radium-223: Radium-223 at a dose of 55 kBq
General disorders Asthenia	25.0% 13/52 • Number of events 13 • Baseline up to 2 years after last dose.
Gastrointestinal disorders Diarrhea	7.7% 4/52 • Number of events 4 • Baseline up to 2 years after last dose.
Gastrointestinal disorders Nausea	7.7% 4/52 • Number of events 4 • Baseline up to 2 years after last dose.
Metabolism and nutrition disorders Anorexia	5.8% 3/52 • Number of events 3 • Baseline up to 2 years after last dose.
Musculoskeletal and connective tissue disorders Athralgia	5.8% 3/52 • Number of events 3 • Baseline up to 2 years after last dose.
Musculoskeletal and connective tissue disorders Bone pain	5.8% 3/52 • Number of events 3 • Baseline up to 2 years after last dose.

Additional Information

Alicia Garcia

MedSIR

Phone: +34 611261467

Email: alicia.garcia@medsir.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place