Prostate CancerPhase 2PSMA-BATNCT04424654
Biomarker Analysis of Castration-resistant Prostate Cancer Undergoing Bipolar Androgen Therapy
A Phase 2 study testing Testosterone cypionate in people with Prostate Cancer, run by Hospital Sirio-Libanes at 2 sites in Brazil.
Trial summary
This is an open label phase II, single-arm, biomarker multi-institutional pilot study. Men with progressive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen deprivation therapy (ADT) and at least one prior second generation AR-targeted therapy (either abiraterone or… 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?
- Testosterone cypionate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesBrazil
- Study dates
- 22 Sep 2020to 1 Jul 2022
- 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
- Willing and able to provide signed informed consent.
- Males aged 18 years of age and above.
- Histological or cytologic proof of adenocarcinoma of the prostate.
- Known castration-resistant disease, defined according to PCWG3 criteria as: castrate serum testosterone level ≤ 50 ng/dL (≤ 1.7 nmol/L). Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through anti-androgen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be 4 weeks.
- Disease progression: serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value within 6 months, each measurement at least 1 week apart, or documented bone lesions by the appearance of ≥ 2 new lesions by bone scintigraphy or dimensionally measurable soft tissue metastatic lesion assessed by CT or MRI.
- Absolute PSA ≥ 1.0 ng/mL at screening.
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- Must have PSA and/or radiographic progression on AT LEAST ONE novel AR- targeted therapy (abiraterone acetate, enzalutamide, apalutamide or darolutamide). One prior chemotherapy agent for mCRPC will be allowed but is not required for inclusion.
- Prior treatment with abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide, and/or ketoconazole is allowed. There is no limit on the maximum number or types of prior hormonal therapies received.
- Must be maintained on a GnRH analogue or have undergone orchiectomy.
- Radiographic evidence of metastatic disease by CT scan and/or bone scan, performed within the prior 6 months
- Karnofsky Performance Status (KPS): ≥ 80% within 14 days before start of study treatment (ECOG < 2)
- Asymptomatic or minimally symptomatic mCRPC according to Brief Pain Inventory - Short Form (BPI-SF) performed during screening: asymptomatic is defined as BPI-SF item #3 score of 0 to 1; minimally symptomatic is defined as BPI-SF item #3 score of 2 to 4.
- Archived tumor tissue obtained prior to enrollment from a metastatic tumor lesion or from a primary tumor lesion (formalin fixed paraffin-embedded [FFPE] block or unstained tumor tissue sections). Tumor sample may be from core biopsy, punch biopsy, excisional biopsy, or surgical specimen).
- Participants must have adequate organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
- Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
- Platelet count ≥ 100 x 109/L
- Total bilirubin within institutional upper limit of normal (ULN) (In patients with Gilbert's syndrome, total bilirubin < 1.5x institutional ULN will be acceptable)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) within institutional upper limit of normal
- Participants must have Creatinine Clearance estimated using the Modified Cockcroft-Gault equation of ≥ 40 mL/min: Estimated Creatinine Clearance = (140-age [years]) x weight (kg) serum creatinine (mg/dL) x 72
- Participants must have a life expectancy ≥ 6 months.
- Male participants and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after the last dose of BAT, to prevent pregnancy in a partner.
- No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).
Who cannot join
- External-beam radiotherapy within the last 4 weeks prior to start of study treatment.
- Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide, darolutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) within the past 4 weeks is not permitted. 5-alpha reductase inhibitor therapies are not allowed as well.
- Prior treatment with chemotherapy for the treatment of metastatic hormone- sensitive prostate cancer is allowed if the last dose of chemotherapy was ≥ 6 months prior to enrollment. In addition, one prior chemotherapy agent for mCRPC will be allowed after a minimum wash-out period of 4 weeks prior to enrollment.
- Patients who have received prior treatment with bipolar androgen therapy (e.g. testosterone, BAT).
- Pain due to metastatic prostate cancer requiring opioid therapy.
- Patients with an intact prostate AND urinary obstructive symptoms are excluded (which includes patients with urinary symptoms from benign prostatic hyperplasia (BPH).
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- Patients receiving anticoagulation therapy are not eligible for study.
- Patients with prior history of an arteriovenous thromboembolic event that occurred within the last 12 months are excluded.
- Participation in another clinical study with an investigational product during the last 4 weeks.
- Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases).
- Concurrent use of other anticancer agents or treatments, with the following exceptions:
- Ongoing treatment with LHRH agonists or antagonists, denosumab or bisphosphonate (e.g. zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
- Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.
- Symptomatic nodal disease, i.e. scrotal, penile or leg edema (CTCAE ≥ Grade 3).
- Patients are excluded if they have active, known brain metastases or leptomeningeal metastases.
- Patients should be excluded if they have an active, known or suspected autoimmune disease (e.g. inflammatory bowel disease, rheumatoid arthritis, autoimmune hepatitis, lupus, celiac disease). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease.
- Permitted therapies include topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed- type hypersensitivity reaction caused by contact allergen) is permitted.
- History of allergy to study drug components.
- Other primary tumor (other than CRPC) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer, low-grade superficial bladder cancer, or cancers that can be cured with local treatment alone).
- Has imminent or established spinal cord compression based on clinical findings and/or MRI.
- Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
- Any uncontrolled major infection.
- Cardiac failure NYHA (New York Heart Association) III or IV.
- Persistent toxicities (CTCAE > Grade 2) caused by previous cancer therapy, excluding alopecia.
- Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 12 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-000
Hospital Sirio-Libanes
São Paulo, 01308050
About this study
Official title: Prospective Biomarker Analysis of Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Undergoing Bipolar Androgen Therapy (BAT)
This is an open label phase II, single-arm, biomarker multi-institutional pilot study. Men with progressive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen deprivation therapy (ADT) and at least one prior second generation AR-targeted therapy (either abiraterone or enzalutamide) will be enrolled in this study. All patients will receive treatment with testosterone cypionate 400 mg, intramuscular, every 28 days for a maximum of 3 cycles or limiting toxicity, if it occurs before the end of the scheduled therapy. After 3 cycles of BAT (12 weeks), patients may continue receiving this therapy off study at the discretion of the treating physician, if clinical/radiographic benefit.
During the study period, patients will have plasma collected for cell-free tumor DNA analysis and CTC ARV7 status and also will perform 68Gallium-PSMA PET at baseline and then every 6 weeks.
- Conditions
- Prostate Cancer
- Being tested
- Testosterone cypionate
- Keywords
- Castration-resistant prostate cancer, Bipolar androgen therapy, PSMA-PET
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone cypionateDrug
Also called Testosterone
Testosterone cypionate 400 mg IM
| Study group | Role | What they receive |
|---|---|---|
| Bipolar Androgen Therapy (BAT) | Experimental | Testosterone cypionate 400 mg IM every 28 days for 3 cycles Receives: Drug: Testosterone cypionate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ga68-PSMA uptake and response to Bipolar Androgen Therapy (BAT)
To evaluate the correlation between baseline Galium68-PSMA/PET maximal standard uptake value (SUVmax) and response to bipolar androgen therapy based on Prostate Cancer Working Group 3 (PCWG3).
Measured: 12 weeks
Secondary outcomes (8)
PSMA SUV kinetics during BAT
To describe the median Galium68-PSMA/PET SUVmax value variation after bipolar androgen therapy
Measured: 12 weeks
ARV7 status and response to BAT
To evaluate the correlation between the AR-V7 status and response to bipolar androgen therapy based on Prostate Cancer Working Group 3 (PCWG3).
Measured: 12 weeks
AR mutational status and response to BAT
To evaluate the correlation between the presence of AR mutations and response to bipolar androgen therapy based on Prostate Cancer Working Group 3 (PCWG3).
Measured: 12 weeks
ARV7 status kinetics during BAT
To describe the ARV7 conversion rate from positive to negative after bipolar androgen therapy.
Measured: 12 weeks
cfDNA kinetics during BAT
To describe the median cfDNA value variation after bipolar androgen therapy
Measured: 12 weeks
Quality of life of patients receiving BAT (BPI-SF)
To evaluate quality of life using the BPI-SF questionnaire before and after BAT.
Measured: 12 weeks
Quality of life of patients receiving BAT (EQ-5D-3L)
To evaluate quality of life using the EQ-5D-3L questionnaire before and after BAT.
Measured: 12 weeks
Quality of life of patients receiving BAT (FACT-P)
To evaluate quality of life using the FACT-P questionnaire before and after BAT.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start22 Sep 2020
- Primary completion1 May 2022
- Study completion1 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Sirio-Libanes
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Moinhos de Vento
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424654
- Sponsor's protocol ID
- HSL-1820
- Acronym
- PSMA-BAT
- Status last verified
- Apr 2021
- First submitted
- 3 Jun 2020
- Last updated
- 3 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gongora ABL, Marshall CH, Velho PI, Lopes CDH, Marin JF, Camargo AA, Bastos DA, Antonarakis ES. Extreme Responses to a Combination of DNA-Damaging Therapy and Immunotherapy in CDK12-Altered Metastatic Castration-Resistant Prostate Cancer: A Potential Therapeutic Vulnerability. Clin Genitourin Cancer. 2022 Apr;20(2):183-188. doi: 10.1016/j.clgc.2021.11.015. Epub 2021 Dec 24. No abstract available.
PubMed 35027313
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Biomarker Analysis of Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Undergoing Bipolar Androgen Therapy (BAT)
- ClinicalTrials.gov ID
- NCT04424654
- Acronym / sponsor ID
- PSMA-BAT / HSL-1820
- Conditions
- Prostate Cancer
- Keywords
- Castration-resistant prostate cancer, Bipolar androgen therapy, PSMA-PET
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hospital Sirio-LibanesUniversity, hospital or other
- Collaborators
- Hospital Moinhos de Vento
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 1 May 2022 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 11 Jun 2020 (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.
This is an open label phase II, single-arm, biomarker multi-institutional pilot study. Men with progressive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen deprivation therapy (ADT) and at least one prior second generation AR-targeted therapy (either abiraterone or enzalutamide) will be enrolled in this study. All patients will receive treatment with testosterone cypionate 400 mg, intramuscular, every 28 days for a maximum of 3 cycles or limiting toxicity, if it occurs before the end of the scheduled therapy. After 3 cycles of BAT (12 weeks), patients may continue receiving this therapy off study at the discretion of the treating physician, if clinical/radiographic benefit.
During the study period, patients will have plasma collected for cell-free tumor DNA analysis and CTC ARV7 status and also will perform 68Gallium-PSMA PET at baseline and then every 6 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bipolar Androgen Therapy (BAT) | Experimental | Drug: Testosterone cypionateTestosterone cypionate 400 mg IM every 28 days for 3 cycles |
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)
- Willing and able to provide signed informed consent.
- Males aged 18 years of age and above.
- Histological or cytologic proof of adenocarcinoma of the prostate.
- Known castration-resistant disease, defined according to PCWG3 criteria as: castrate serum testosterone level ≤ 50 ng/dL (≤ 1.7 nmol/L). Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through anti-androgen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be 4 weeks.
- Disease progression: serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value within 6 months, each measurement at least 1 week apart, or documented bone lesions by the appearance of ≥ 2 new lesions by bone scintigraphy or dimensionally measurable soft tissue metastatic lesion assessed by CT or MRI.
Key exclusion criteria (26 listed)
- External-beam radiotherapy within the last 4 weeks prior to start of study treatment.
- Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide, darolutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) within the past 4 weeks is not permitted. 5-alpha reductase inhibitor therapies are not allowed as well.
- Prior treatment with chemotherapy for the treatment of metastatic hormone- sensitive prostate cancer is allowed if the last dose of chemotherapy was ≥ 6 months prior to enrollment. In addition, one prior chemotherapy agent for mCRPC will be allowed after a minimum wash-out period of 4 weeks prior to enrollment.
- Patients who have received prior treatment with bipolar androgen therapy (e.g. testosterone, BAT).
- Pain due to metastatic prostate cancer requiring opioid therapy.
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 |
|---|---|---|
| Testosterone cypionateAlso: TestosteroneTestosterone cypionate 400 mg IM | Drug | Bipolar Androgen Therapy (BAT) |
Primary outcome
Ga68-PSMA uptake and response to Bipolar Androgen Therapy (BAT)
Time frame: 12 weeks
To evaluate the correlation between baseline Galium68-PSMA/PET maximal standard uptake value (SUVmax) and response to bipolar androgen therapy based on Prostate Cancer Working Group 3 (PCWG3).
8 secondary outcomes
PSMA SUV kinetics during BAT
Time frame: 12 weeks
ARV7 status and response to BAT
Time frame: 12 weeks
AR mutational status and response to BAT
Time frame: 12 weeks
ARV7 status kinetics during BAT
Time frame: 12 weeks
cfDNA kinetics during BAT
Time frame: 12 weeks
Quality of life of patients receiving BAT (BPI-SF)
Time frame: 12 weeks
Quality of life of patients receiving BAT (EQ-5D-3L)
Time frame: 12 weeks
Quality of life of patients receiving BAT (FACT-P)
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
- Derived from this study: PubMed 35027313Gongora ABL, Marshall CH, Velho PI, Lopes CDH, Marin JF, Camargo AA, Bastos DA, Antonarakis ES. Extreme Responses to a Combination of DNA-Damaging Therapy and Immunotherapy in CDK12-Altered Metastatic Castration-Resistant Prostate Cancer: A Potential Therapeutic Vulnerability. Clin Genitourin Cancer. 2022 Apr;20(2):183-188. doi: 10.1016/j.clgc.2021.11.015. Epub 2021 Dec 24. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 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 Testosterone cypionate in people with Prostate Cancer, run by Hospital Sirio-Libanes at 2 sites 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 26 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 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Ga68-PSMA uptake and response to Bipolar Androgen Therapy (BAT) (time frame: 12 weeks). 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 NCT04424654, 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 3 Aug 2022.