Prostate CancerPhase 2NCT05900973
A Phase 2 Trial of Darolutamide as a Prostate-Specific Membrane Antigen (PSMA) Expression Enhancer in Patients With Localized Prostate Cancer
A Phase 2 study testing Darolutamide Oral Tablet [Nubeqa] in people with Prostate Cancer, run by D'Or Institute for Research and Education at 1 site in Brazil.
Trial summary
Prostate cancer is the second leading cause of cancer death in men. According to estimates by the American Cancer Society Prostate for 2022, about 268,490 men would be diagnosed with prostate cancer and 34,500 would die from the disease. 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?
- Darolutamide Oral Tablet [Nubeqa]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteBrazil
- Study dates
- 20 Jul 2023to 24 May 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- To be included in this study, patients should complete all screening procedures and meet all of the following criteria:
- Males 18 years of age and above
- Histologically or cytologically proven diagnosis of prostate adenocarcinoma
- High-risk disease defined as at least one of the following factors:
- Gleason ≥8
- PSA ≥20 ng/mL
Show all 23Show fewer
- T3/T4 disease
- ECOG Performance status of 0 or 1 (Appendix A: Performance Status Criteria)
- Patients deemed appropriate candidates for radical prostatectomy
- Baseline blood pressure <160 x 100 mmHg
- Normal hematologic, liver, and renal functions
- Absence of any contraindications for darolutamide use
- Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
- Baseline testosterone of 200 ng/dL or more
- Normal organ function with acceptable initial laboratory values within 14 days of treatment start: Match lab values to those scheduled in Table 1.
- ANC • > 1,500/µl
- Hemoglobin • > 9g/dL
- Platelet count • > 100,000/µl
- Creatinine • ≤ 1.5 x the institutional upper limit of normal (ULN)
- Potassium • > 3.5 mmol/L (within institutional normal range)
- Bilirubin • ≤ ULN (unless documented Gilbert's disease)
- SGOT (AST) • ≤ 2.5 x ULN
- SGPT (ALT) • ≤ 2.5 x ULN
Who cannot join
- Metastatic disease defined by standard scans (bone scans, magnetic resonance, or CT scans)
- Any prior or current treatment for prostate cancer
- Concomitant treatment with another systemic antineoplastic therapy or another investigational product is prohibited, as follows:
- Any investigational product
- Radiopharmaceuticals
- Immunotherapy (e.g. sipuleucel-T)
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- Prior orchiectomy or any LHRH agonist or antagonist
- Cytotoxic chemotherapy
- Enzalutamide, apalutamide, bicalutamide, flutamide, nilutamide
- Estrogens
- Cyproterone acetate
- 5-alpha-reductase inhibitors
- Abiraterone acetate, TAK-700 or other CYP17 inhibitors
- Systemic ketoconazole
- Any drug listed in Appendix C
- Patients on current treatment for a second malignancy (except for Ta bladder urothelial carcinoma or non-melanoma skin cancer).
- Uncontrolled hypertension (defined as systolic blood pressure of 150 mmHg or higher; diastolic blood pressure of 100 mmHg or higher in 2 or more measurements) or uncompensated cardiac disease (NYHA III or IV)
- Known allergy, hypersensitivity, any other contraindications to the compounds under investigation (darolutamide or PSMA radiotracers)
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Instituto D'Or de Pesquisa e Ensino
São Paulo
José M Mota, MD, PhD
About this study
Prostate cancer is the second leading cause of cancer death in men. According to estimates by the American Cancer Society Prostate for 2022, about 268,490 men would be diagnosed with prostate cancer and 34,500 would die from the disease. Clinical evolution follows the clinical stages are: localized disease, biochemical recurrence after surgery or radiotherapy, and castration-sensitive or castration-resistant metastatic disease. Localized disease is often classified according to a risk stratification system, which includes assessment of the Gleason score, prostate-specific antigen (PSA) at diagnosis, number of involved fragments per disease at biopsy, and clinical T-staging. Gleason score greater than or equal to 8, PSA greater than or equal to 20 ng/dL at diagnosis, and/or involvement of the prostatic capsule or seminal vesicle are high-risk criteria for biochemical recurrence and later development of metastases, for which the standard treatment is radical prostatectomy or radiotherapy plus androgen deprivation therapy. Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of prostate cancer cells, with relatively low expression in normal tissue. PSMA has been explored as a target in imaging studies using positron emission tomography (PSMA-PET) to reveal occult metastatic disease, as well as a target in the development of PSMA-based treatments with radioligands. According to Hoffman et al., performing PSMA-PET demonstrated greater sensitivity (85% vs. 38%) and specificity (98% vs. 91%), and determined more changes in patient management (28% vs. 15% ) compared to conventional images. Other studies have also demonstrated the greater accuracy of PSMA-based radiotracers compared to conventional images. Finding strategies that increase PSMA expression is a necessity for patients with prostate cancer. According to researchers, high SUVmax values are associated with better outcomes in patients treated with 177-lutetium-PSMA-617. PSMA expression can be rapidly modulated by androgen suppression. The investigators understand that there is great potential to evaluate darolutamide as a PSMA expression enhancer. However, to date there are no prospective data evaluating the effect of ARSI in increasing PSMA expression in localized disease. Here the investigators propose a phase 2 study to investigate the efficacy of a limited course of darolutamide as a PSMA expression enhancer in men with localized prostate cancer according to conventional imaging. PSMA-PET/CT scans will be acquired before and after treatment with darolutamide, as detailed in the protocol. Slides of prostate biopsies and prostatectomies stained with hematoxylin and eosin (H\&E) will be reviewed by two pathologists to select the most representative tumor block. Immunohistochemical (IHC) reaction using standard protocols will be performed using an anti-PSMA antibody and intraprostatic anti-androgens. Gene expression analysis will be performed using RNA extracted from biopsies and prostatectomies and evaluated by a panel of over 300 transcripts. For methylation patterns, hematoxylin and eosin (H\&E) slides from prostate biopsies and prostatectomies will undergo DNA extraction and evaluation of the methylation profile performed using a kit. It is expected to identify that treatment with darolutamide increases PSMA expression and that the biochemical mechanisms involved can be better evidenced.
- Conditions
- Prostate Cancer
- Being tested
- Darolutamide Oral Tablet [Nubeqa]
- Keywords
- prostate cancer, PET PSMA, Prostate-specific membrane antigen (PSMA), Darolutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darolutamide Oral Tablet [Nubeqa]Drug
Oral use of Darolutamide as an Inducer of Increased Expression of Prostate-specific membrane antigen (PSMA) in patients with Localized prostate cancer
| Study group | Role | What they receive |
|---|---|---|
| NUBEQA® (darolutamide) administered to participants | Experimental | Oral use of Darolutamide as an Inducer of Increased Expression of Prostate-specific membrane antigen (PSMA) in patients with Localized prostate cancer Receives: Drug: Darolutamide Oral Tablet [Nubeqa] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intraindividual pre- and post-treatment SUVmax.
The proportion of patients achieving an increase in the SUVmax of 20% or higher will be reported with two-sided 90% confidence interval (corresponding to the one-sided α=0.05 in the statistical design) that accounts for the two-stage design.
Measured: 7 days
Secondary outcomes (4)
Increase of PSMA-PET/CT parameters
PSMA PET/CT pre- and post-treatment will also be reported with 90% exact binomial CI.
Measured: 7 days
Detection rate of extrapelvic metastatic disease pre- and post-darolutamide
The proportion of patients with planned management changes accordingly to PSMA PET/CT pre- and post-treatment will also be reported with 90% exact binomial CI. Any lesion with an SUV greater than the hepatic background will be considered a PSMA-positive lesion.
Measured: 7 days
Detection rate of pelvic nodal metastatic disease pre- and post- darolutamide.
The proportion of patients with planned management changes accordingly to PSMA PET/CT pre- and post-treatment will also be reported with 90% exact binomial CI. Any lesion with an SUV greater than the hepatic background will be considered a PSMA-positive lesion.
Measured: 7 days
Proportion of planned management changes with PSMA PET pre- and post- darolutamide.
The proportion of patients with planned management changes accordingly to PSMA PET/CT pre- and post-treatment will also be reported with 90% exact binomial CI. Treatment decisions will be made at physician's discretion.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study start20 Jul 2023
- Primary completion17 May 2025 (estimated)
- Study completion24 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- D'Or Institute for Research and Education
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, RPH Central Pharma
- Responsible party
- Sponsor
- Investigators
- José Mauricio SC Mota, phD, Principal investigator, Instituto D'Or de Pesquisa e Ensino (IDOR), São Paulo, Brazil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05900973
- Sponsor's protocol ID
- ID 389-22-ONCO-FOMENTO-SP
- Status last verified
- Aug 2023
- First submitted
- 8 May 2023
- Last updated
- 7 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Records must be retained and securely stored until: (a) two (2) years after the date of approval of a new drug application for the study drug that is the subject of the clinical trial; or (b) two (2) years after the investigational new drug order for such study drug is closed or withdrawn, or for such longer period of time as may be required by participant policies, applicable laws, rules or regulations.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Darolutamide as a Prostate-Specific Membrane Antigen (PSMA) Expression Enhancer in Patients With Localized Prostate Cancer
- ClinicalTrials.gov ID
- NCT05900973
- Acronym / sponsor ID
- ID 389-22-ONCO-FOMENTO-SP
- Conditions
- Prostate Cancer
- Keywords
- prostate cancer, PET PSMA, Prostate-specific membrane antigen (PSMA), Darolutamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- D'Or Institute for Research and EducationUniversity, hospital or other
- Collaborators
- Bayer, RPH Central Pharma
- Study start
- 20 Jul 2023 (actual)
- Primary completion
- 17 May 2025 (estimated)
- Study completion
- 24 May 2025 (estimated)
- First posted
- 13 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prostate cancer is the second leading cause of cancer death in men. According to estimates by the American Cancer Society Prostate for 2022, about 268,490 men would be diagnosed with prostate cancer and 34,500 would die from the disease. Clinical evolution follows the clinical stages are: localized disease, biochemical recurrence after surgery or radiotherapy, and castration-sensitive or castration-resistant metastatic disease. Localized disease is often classified according to a risk stratification system, which includes assessment of the Gleason score, prostate-specific antigen (PSA) at diagnosis, number of involved fragments per disease at biopsy, and clinical T-staging. Gleason score greater than or equal to 8, PSA greater than or equal to 20 ng/dL at diagnosis, and/or involvement of the prostatic capsule or seminal vesicle are high-risk criteria for biochemical recurrence and later development of metastases, for which the standard treatment is radical prostatectomy or radiotherapy plus androgen deprivation therapy. Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of prostate cancer cells, with relatively low expression in normal tissue. PSMA has been explored as a target in imaging studies using positron emission tomography (PSMA-PET) to reveal occult metastatic disease, as well as a target in the development of PSMA-based treatments with radioligands. According to Hoffman et al., performing PSMA-PET demonstrated greater sensitivity (85% vs. 38%) and specificity (98% vs. 91%), and determined more changes in patient management (28% vs. 15% ) compared to conventional images. Other studies have also demonstrated the greater accuracy of PSMA-based radiotracers compared to conventional images. Finding strategies that increase PSMA expression is a necessity for patients with prostate cancer. According to researchers, high SUVmax values are associated with better outcomes in patients treated with 177-lutetium-PSMA-617. PSMA expression can be rapidly modulated by androgen suppression. The investigators understand that there is great potential to evaluate darolutamide as a PSMA expression enhancer. However, to date there are no prospective data evaluating the effect of ARSI in increasing PSMA expression in localized disease. Here the investigators propose a phase 2 study to investigate the efficacy of a limited course of darolutamide as a PSMA expression enhancer in men with localized prostate cancer according to conventional imaging. PSMA-PET/CT scans will be acquired before and after treatment with darolutamide, as detailed in the protocol. Slides of prostate biopsies and prostatectomies stained with hematoxylin and eosin (H\&E) will be reviewed by two pathologists to select the most representative tumor block. Immunohistochemical (IHC) reaction using standard protocols will be performed using an anti-PSMA antibody and intraprostatic anti-androgens. Gene expression analysis will be performed using RNA extracted from biopsies and prostatectomies and evaluated by a panel of over 300 transcripts. For methylation patterns, hematoxylin and eosin (H\&E) slides from prostate biopsies and prostatectomies will undergo DNA extraction and evaluation of the methylation profile performed using a kit. It is expected to identify that treatment with darolutamide increases PSMA expression and that the biochemical mechanisms involved can be better evidenced.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NUBEQA® (darolutamide) administered to participants | Experimental | Drug: Darolutamide Oral Tablet [Nubeqa]Oral use of Darolutamide as an Inducer of Increased Expression of Prostate-specific membrane antigen (PSMA) in patients with Localized prostate cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- To be included in this study, patients should complete all screening procedures and meet all of the following criteria:
- Males 18 years of age and above
- Histologically or cytologically proven diagnosis of prostate adenocarcinoma
- High-risk disease defined as at least one of the following factors:
- Gleason ≥8
Key exclusion criteria (18 listed)
- Metastatic disease defined by standard scans (bone scans, magnetic resonance, or CT scans)
- Any prior or current treatment for prostate cancer
- Concomitant treatment with another systemic antineoplastic therapy or another investigational product is prohibited, as follows:
- Any investigational product
- Radiopharmaceuticals
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 |
|---|---|---|
| Darolutamide Oral Tablet [Nubeqa]Oral use of Darolutamide as an Inducer of Increased Expression of Prostate-specific membrane antigen (PSMA) in patients with Localized prostate cancer | Drug | NUBEQA® (darolutamide) administered to participants |
Primary outcome
Intraindividual pre- and post-treatment SUVmax.
Time frame: 7 days
The proportion of patients achieving an increase in the SUVmax of 20% or higher will be reported with two-sided 90% confidence interval (corresponding to the one-sided α=0.05 in the statistical design) that accounts for the two-stage design.
4 secondary outcomes
Increase of PSMA-PET/CT parameters
Time frame: 7 days
Detection rate of extrapelvic metastatic disease pre- and post-darolutamide
Time frame: 7 days
Detection rate of pelvic nodal metastatic disease pre- and post- darolutamide.
Time frame: 7 days
Proportion of planned management changes with PSMA PET pre- and post- darolutamide.
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
- Individual participant dataSharing planned: Yes. Records must be retained and securely stored until: (a) two (2) years after the date of approval of a new drug application for the study drug that is the subject of the clinical trial; or (b) two (2) years after the investigational new drug order for such study drug is closed or withdrawn, or for such longer period of time as may be required by participant policies, applicable laws, rules or regulations.
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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.
José Mauricio SC Mota, phD principal investigator
Instituto D'Or de Pesquisa e Ensino (IDOR), São Paulo, Brazil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darolutamide Oral Tablet [Nubeqa] in people with Prostate Cancer, run by D'Or Institute for Research and Education at 1 site in Brazil.
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 23 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact José Mauricio SC Mota, MD, PhD (+551121098855 ext. 8855, jose.cmota@oncologiador.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intraindividual pre- and post-treatment SUVmax. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2023.