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

NCT03002220 | Completed Phase 2 Results

• 2 other identifiers: MedOPP0982016-001888-36
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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 (9)

• AEs and Serious Adverse Events (SAEs)

  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.

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

• Overall Survival (OS).

  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).

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

• Time to PSA Progression According to the ALSYMPCA Study Criteria.

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

Study Arms (1)

open-label

EXPERIMENTAL

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

radium-223 DRUG

Radium-223 at a dose of 55 kBq

Also known as: Xofigo

open-label

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• MedSIR: lead
• Bayer: collaborator

Study Sites (6)

MedSIR Investigative site

Barcelona, Spain

Location

MedSIR Investigative site

Cáceres, Spain

Location

MedSIR Investigative site

Córdoba, Spain

Location

MedSIR Investigative site

Lugo, Spain

Location

MedSIR Investigative site

Madrid, Spain

Location

MedSIR investigative site

Palma de Mallorca, 07120, Spain

Location

Related Publications (1)

• 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.

  PMID: 35981452 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radium-223; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

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.

Results Point of Contact

• Title: Alicia Garcia
• Organization: MedSIR

alicia.garcia@medsir.org

+34 611261467

Study Officials

• Joan Carles Galcerán

  H. Vall Hebrón

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: December 23, 2016
• Study Start: December 21, 2016
• Primary Completion: May 6, 2020
• Study Completion: June 9, 2021
• Last Updated: December 11, 2024
• Results First Posted: December 11, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)