Prostate CancerPhase 2EXCAAPENCT03002220
Trial of Rad-223 Activity in Asymptomatic Patients With mCRPC While on Abiraterone or Enzalutamide Besides AR-V7 Status
A Phase 2 study testing radium-223 in people with Prostate Cancer, run by MedSIR at 6 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- radium-223
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 6 sitesSpain
- Study dates
- 21 Dec 2016to 9 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
MedSIR Investigative site
Barcelona
MedSIR Investigative site
Cáceres
MedSIR Investigative site
Córdoba
MedSIR Investigative site
Lugo
MedSIR Investigative site
Madrid
MedSIR investigative site
Palma de Mallorca, 07120
About this study
Official title: A Phase II Clinical Trial of Radium-223 Activity in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) With Asymptomatic Progression While on Abiraterone Acetate or Enzalutamide Besides AR-V7 Mutational Status
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
- Prostate Cancer
- Being tested
- radium-223
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radium-223Drug
Also called Xofigo
Radium-223 at a dose of 55 kBq
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: radium-223 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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.
Measured: From date of inclusion until Radiographic progression, assessed up to 20 months
Overall Survival (OS).
Measured: 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.
Measured: From date of first drug administration until SSE, assessed up to 20 months
Time to PSA Progression According to the ALSYMPCA Study Criteria.
Measured: 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).
Measured: 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
Measured: From date of first study drug administration until End of Treatment, assessed up to 6 months
Assessment of AR-V7 Mutation Evolution
Measured: 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.
Measured: From date of first study drug administration until End of Treatment, assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2016 (estimated)
- Study start21 Dec 2016
- Primary completion6 May 2020
- Study completion9 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedSIR
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Joan Carles Galcerán, Study director, H. Vall Hebrón
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03002220
- Sponsor's protocol ID
- MedOPP098
- Other IDs
- 2016-001888-36, 2016
- Acronym
- EXCAAPE
- Status last verified
- Oct 2024
- First submitted
- 20 Oct 2016
- Last updated
- 11 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Radium-223 Activity in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) With Asymptomatic Progression While on Abiraterone Acetate or Enzalutamide Besides AR-V7 Mutational Status
- ClinicalTrials.gov ID
- NCT03002220
- Acronym / sponsor ID
- EXCAAPE / MedOPP098
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- MedSIRUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 21 Dec 2016 (actual)
- Primary completion
- 6 May 2020 (actual)
- Study completion
- 9 Jun 2021 (actual)
- First posted
- 23 Dec 2016 (estimated)
- Results
- Posted 11 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| open-label | Experimental | Drug: radium-223Patient 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| radium-223Also: XofigoRadium-223 at a dose of 55 kBq | Drug | open-label |
Primary outcome
Assess the Efficacy of Radium-223 in Terms of Radiological rPFS
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
The primary efficacy endpoint is the median PFS (evaluated using RECIST v1.1) achieved with radium-223 treatment
9 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 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
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
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
Time frame: From date of first study drug administration until End of Treatment, assessed up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35981452Carles 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joan Carles Galcerán study director
H. Vall Hebrón
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing radium-223 in people with Prostate Cancer, run by MedSIR at 6 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the Efficacy of Radium-223 in Terms of Radiological rPFS (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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03002220, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.