Prostate Cancer

Condition: Primary Malignant Neoplasm of Prostate (Diagnosis)

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04797039

Sponsor: Mayo Clinic

Phase:

Eligibility:

• Age: minimum 30 Years maximum 100 Years
• Gender: Male

Inclusion Criteria:

• Patients with "biopsy proven" Gleason7 prostate cancer referred to Urology and/or Interventional Radiology for treatment
• Surgery and/or Radiation is not a desirable alternative therapy at the time of enrollment
• Tumor size is < 2 cm at its largest diameter
• Tumor does not encompass the rectal wall or external urethral sphincter
• Patient is able to undergo MRI

Exclusion Criteria:

1. •

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Condition: Prostatic Neoplasm, Prostatic Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT04484701

Sponsor: British Columbia Cancer Agency

Phase:

Eligibility:

• Age: minimum 19 Years maximum 99 Years
• Gender: Male

Inclusion Criteria:

• Eastern Cooperative Oncology Group performance status of 2 or less.
• Subjects with high risk prostate cancer (CAPRA score 6 or higher) being considered for curative-intent surgery or radiation therapy (including brachytherapy)
• Subjects with biopsy confirmed prostate cancer being considered for curative-intent surgery or radiation therapy (including brachytherapy), who have unconfirmed suspicious findings on conventional medical imaging staging examinations.
• Subjects with biochemical recurrence or persistence of prostate cancer following initial curative treatment by radical prostatectomy, with two consecutive PSA values >0.2 ng/ml measured more than 6 weeks after radical prostatectomy. If subjects received subsequent systemic therapy, the most recent PSA measurement prior to PET/CT imaging must be greater than 0.2 ng/mL.
• Subjects with biochemical recurrence or persistence of prostate cancer following initial curative treatment by radical prostatectomy and subsequently treated by salvage radiotherapy or pelvic node dissection, with two consecutive PSA values >0.2 ng/ml. If subjects received subsequent systemic therapy, the most recent PSA measurement prior to PET/CT imaging must be greater than 0.2 ng/mL.
• Subjects with biochemical recurrence of prostate cancer after initial curative therapy with radiation therapy (including brachytherapy), or non-standard local ablative therapy (such as high frequency ultrasound, cryoablation, focal laser ablation, etc.), with a PSA level >2 ng/mL above the nadir after radiation therapy.
• Subjects with advanced castration sensitive or castration resistant prostate cancer being considered for localized treatment (surgery, brachytherapy, radiotherapy) of recurrent or oligometastatic prostate cancer. Castration resistance is defined as a PSA level > 1.0 ng/mL, with 2 consecutive rises above the nadir, in the presence of castrate levels of testosterone (< 1.7 nmol/L).
• Subjects with metastatic or castration resistant prostate cancer being evaluated for systemic therapy administered in therapeutic clinical trials. The PSA level must be > 1.0 ng/mL, with 2 consecutive rises above the nadir, in the presence of castrate levels of testosterone (< 1.7 nmol/L). Exclusion Criteria:
• Medically unstable (e.g. acute illness, unstable vital signs)
• Unable to lie supine for the duration of imaging
• Unable to provide written consent
• Exceeds safe weight limit of the PET/CT bed (204.5 kg) or unable to fit through the PET/CT bore (diameter 70 cm)

Exclusion Criteria:

• Medically unstable (e.g. acute illness, unstable vital signs)
• Unable to lie supine for the duration of imaging
• Unable to provide written consent
• Exceeds safe weight limit of the PET/CT bed (204.5 kg) or unable to fit through the PET/CT bore (diameter 70 cm) Exclusion criteria for the use of furosemide Subjects can still participate in the research study and undergo the [68Ga]Ga-PSMA-11 scan if they are unable or unwilling to receive a furosemide injection.
• Subjects with end stage renal disease.
• Subjects with documented history of severe progressive chronic kidney disease (glomerular filtration rate less than 30 mL/min/1.73 m2).
• Subjects with hypersensitivity to furosemide (Lasix).
• While cross-reactivity between sulfonamide antibiotics and non-antibiotics has been disproven, subjects who have a history of sulfonamide antibiotics or sulfonylureas may be at a higher risk of allergic reaction to furosemide due to a higher general predisposition to allergic reactions. In those instances, the administration of furosemide is left at the discretion of the local site investigator after discussion with the study subject.
• Subjects with severe hypokalemia, hyponatremia, hypovolemia, dehydration or hypotension.
• Subjects with untreated bladder outlet obstruction or lower urinary tract symptoms, who have a history of obstructive episodes that required hospitalization, emergency department visits and/or bladder catheterization for relief of symptoms.

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Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05714774

Sponsor: Hospices Civils de Lyon

Eligibility:

• Age: minimum 50 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patient who has been clearly informed of the study and has agreed, with sufficient time for reflection, to participate by signing the study informed consent form.
• Male aged ≥ 50 years,
• PSA ≤ 15 ng/mL
• diagnosis of localized prostate cancer (stage T1 or T2) with a Gleason score of ≤ 7
• Focal, hemiablation or ablation HIFU treatment validated in Multidisciplinary Concerted Meeting
• Patient enrolled in Medicare or equivalent plan.
• Interpretable preoperative multiparametric MRI performed within 180 days prior to surgery

Exclusion Criteria:

• an ASA score >3
• brachytherapy for prostate cancer
• Person of full age protected by law (person under guardianship or curatorship).
• Contraindication to HIFU treatment as defined in the Focal One instructions for use :
• Multiple intraprostatic calcifications inducing, on ultrasound, a shadow cone in the prostate preventing the penetration of ultrasound and therefore the realization of the treatment.
• Presence of permanent radioactive implants in the rectal wall.
• Presence of an implant (stent, catheter) located less than 1 cm from the treatment area.
• Fistula of the urinary tract or rectum.
• Anal or rectal fibrosis, anal or rectal stenosis or other abnormalities making insertion of the Focal One® catheter difficult.
• Anatomical abnormality of the rectum or rectal mucosa.
• Patient with an artificial sphincter, penile prosthesis or intraprostatic implant, such as a stent.
• History of inflammatory bowel disease.
• Current urogenital infection (infection should be treated prior to HIFU treatment).
• Patient allergic to latex with known severe reactionsCounter-indications to anesthesia

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Condition: Prostate Cancer, Cancer of Prostate

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04887935

Sponsor: Washington University School of Medicine

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologically or cytologically confirmed localized prostatic adenocarcinoma. Patients with primarily neuroendocrine/small cell histology will be excluded.
• Patients with high risk or very high risk prostatic adenocarcinoma as defined by NCCN criteria.
• High risk is defined by NCCN as meeting at least one of the following criteria:
• T3a
• grade group 4 or 5
• PSA > 20
• Very high risk is defined by NCCN as meeting at least one of the following criteria:
• T3b-T4
• primary Gleason pattern 5
• 2-3 high risk features **> 4 cores with grade group 4 or 5
• Willing and able to undergo prostate MRI at baseline, with a measurable prostate lesion present.
• Planning to undergo radical prostatectomy as primary treatment for localized prostate cancer.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate bone marrow and organ function as defined below:
• Leukocytes ≥ 3.0 K/cumm
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m^2
• Agreement to adhere to Lifestyle Considerations throughout study duration
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Current or previous treatment with SGLT2i or thiazolidinedione.
• Currently receiving regularly scheduled systemic steroids in the form of prednisone or dexamethasone (more than 10 mg prednisone daily or equivalent). Topical steroid ointments or creams for occasional skin rash is allowed.
• A history of other malignancy with the exceptions of malignancies for which all treatment was completed at least 2 years before registration with no evidence of disease and locally treated skin squamous or basal cell carcinoma.
• History of stroke or transient ischemic attack in the last 5 years.
• Patients with type 1 diabetes mellitus will be excluded or patients with insulin-requiring diabetes mellitus will be excluded. Only patients with well-controlled type 2 diabetes mellitus will be allowed.
• Screening HbA1c > 10%, unless approved by endocrinologist.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dapagliflozin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, peripheral arterial disease, ketoacidosis, severe kidney disease (estimated glomerular filtration rate eGFR < 30 mL/min/1.73m2), symptomatic hypotension, and chronic/frequent urinary tract infections or yeast infections.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
• Any evidence of pelvic instrumentation (i.e. hip arthroplasty) that would obscure and/or limit prostate MRI evaluation at the discretion of the investigator, or any type of medical device that would be incompatible with MRI imaging.

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Condition: Prostatic Neoplasms

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03805919

Sponsor: National Cancer Institute (NCI)

Phase:

Eligibility:

• Age: minimum 30 Years maximum 75 Years
• Gender: Male

Inclusion Criteria:

• Persons assigned male at birth between the ages of 30-75 years.
• Documented germline variant (i.e. pathogenic/likely pathogenic variant) in prostate cancer risk-related gene from a CLIA certified laboratory: BRCA1 and BRCA2, MMR genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome, as well as HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).
• Prognosis of >5 years survival if affected by another cancer
• Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior diagnosis or treatment for prostate cancer
• Known contraindication to MRI:
• Participants unable to fit through MRI scanner (radiologist discretion)
• Allergy to MR contrast agent
• Participants with pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic device
• Active concomitant medical or psychological illnesses that may increase the risk to the subject or inability to obtain informed consent, at the discretion of the principal investigator.

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Condition: Metastatic Castration-resistant Prostate Cancer (mCRPC), Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06136650

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• The main inclusion criteria include but are not limited to the following:
• Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography scan (CT)/magnetic resonance imaging (MRI)
• Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening
• Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) metastatic hormone sensitive prostate cancer (mHSPC) or non metastatic hormone sensitive prostate cancer (nmHSPC), for at least 8 weeks (at least 14 weeks for participants with bone progression) Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than six cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
• Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
• Has had prior treatment with Poly polymerase inhibitors (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
• Has adequate organ function
• Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening
• Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy (HRT) or participants who have ≤Grade 2 neuropathy are eligible
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) Exclusion Criteria: The main

Exclusion Criteria:

• The main exclusion criteria include but are not limited to the following:
• Has presence of gastrointestinal condition
• Is unable to swallow capsules/tablets
• Has history of pituitary dysfunction
• Has poorly controlled diabetes mellitus
• Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
• Has clinically significant abnormal serum potassium or sodium level
• Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) <110 mmHg, or Uncontrolled hypertension: systolic BP >160mmHg or diastolic blood BP >90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy
• History or family history of long QTc syndrome
• Has a history of seizure(s) within 6 months prior to signing the informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment
• Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place
• Has received a taxane-based chemotherapy and or NHA for metastatic castration-resistant prostate cancer (mCRPC)
• Has not adequately recovered from major surgery or have ongoing surgical complications
• Has received prior treatment with radium for prostate cancer
• Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures
• Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
• Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids
• Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
• Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention
• Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat.
• Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention
• Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed
• Active infection requiring systemic therapy
• Has concurrent active Hepatitis B virus and Hepatitis C virus infection

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Condition: Prostate Cancer Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06136624

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

• Age: minimum N/A maximum N/A
• Gender: All

Inclusion Criteria:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before Screening
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has disease that progressed during or after treatment with 1 novel hormonal agent (NHA)
• Has received 1 but no more than 2 taxane-based chemotherapy regimens for metastatic castration-resistant prostate cancer (mCRPC) and has had progressive disease (PD) during or after treatment
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
• Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
• Has had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
• Has received prior 177Lu-PSMA-617 or were deemed ineligible to receive 177Lu-PSMA-617 treatment by the investigator or refused 177Lu-PSMA-617 treatment
• Participants who have not received cabazitaxel can be enrolled if they are ineligible for cabazitaxel treatment as determined by the investigator or have refused treatment
• If participant received first generation anti-androgen therapy before screening, the participant has evidence of disease progression >4 weeks since the last flutamide treatment and >6 weeks since the last bicalutamide or nilutamide treatment
• Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥ 4 weeks before the date of randomization
• Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on antiretroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening.
• Participants who can produce sperm must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat, for at least 30 days after the last dose of abiraterone acetate, and for at least 3 months after the last dose of enzalutamide: EITHER be abstinent OR must agree to use male condom

Exclusion Criteria:

• Has a gastrointestinal disorder that might affect absorption
• Has a history of pituitary dysfunction
• Has poorly controlled diabetes mellitus
• Has clinically significant abnormal serum potassium or sodium level
• Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
• Has a history of seizure within 6 months of providing documented informed consent or any condition that may predispose to seizures within 12 months before the date of randomization
• Has a history of clinically significant ventricular arrhythmias
• Has received an anticancer monoclonal antibody (mAb) within 4 weeks before the date of randomization, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of randomization
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications
• Has used herbal or medicinal products that may have hormonal anti-prostate cancer activity and/or are known to decrease prostate-specific Antigen (PSA) (eg, saw palmetto, megesterol acetate) within 4 weeks before the date of randomization
• Has received radium-223 or lutetium-177 within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline from AEs due to radium-223 or lutetium-177 administered more than 4 weeks before the date of randomization
• Has received treatment with 5-αreductase inhibitors (eg, finasteride or dutasteride), estrogens, or cyproterone within 4 weeks before the date of randomization
• Has received colony-stimulating factors within 28 days before the date of randomization
• Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days of the date of randomization
• Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate + prednisone or darolutamide within 2 weeks
• Has a "superscan" bone scan
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has an active infection requiring systemic therapy
• Has concurrent active HBV or known active HCV infection
• Has a history of long QTc syndrome
• Has any of the following at Screening Visit: hypotension (systolic BP <110 mm Hg) or uncontrolled hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 out of 3 recordings with optimized antihypertensive therapy)
• Is unable to swallow capsules/tablets
• Is currently being treated with cytochrome 450-inducing antiepileptic drugs for seizures
• Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Systemic use of the following medications within 2 weeks before the first dose of study intervention: strong CYP3A4 inducers (eg, avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, or St John's Wort); P-gp inhibitors (eg, erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, or milk thistle [Silybum marianum])
• Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention

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Condition: Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06136598

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Exclusion Criteria:

1. include but are not limited to the following:

Inclusion Criteria:

• Has histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Has prostate cancer while receiving androgen deprivation therapy (ADT), or post-bilateral orchiectomy, within 6 months before screening.
• Has evidence of progression >4 weeks since last flutamide treatment or >6 weeks since last bicalutamide or nilutamide treatment.
• Has evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue shown by CT/MRI.
• Has disease that progressed during or after treatment with at least 1 line of next-generation hormonal agents (NHAs) for hormone-sensitive prostate cancer (HSPC) or castration-resistant prostate cancer (CRPC) for at least 8 weeks (at least 14 weeks for participants with bone progression).
• Has received at least 1 line of taxane-based chemotherapy for HSPC or CRPC and have had progressed disease during or on treatment, or refused or ineligible to receive chemotherapy.
• Has a life expectancy of >3 months. Exclusion Criteria:
• Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
• Has presence of gastrointestinal condition, e.g. malabsorption, that might affect the adsorption of study intervention.
• Has a history of pituitary dysfunction.
• Has poorly controlled diabetes mellitus.
• Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 4 weeks of the date of allocation.
• Has received an anticancer monoclonal antibody (mAb) within 4 weeks of allocation, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of allocation.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the date of allocation.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to the start of study intervention.
• Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of or current human immunodeficiency virus (HIV) infection.
• Has a concurrent Hepatitis B or Hepatitis C virus infection.
• Has a history of allogenic tissue or solid organ transplant.

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Condition: Prostate Cancer, Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06056830

Sponsor: Clarity Pharmaceuticals Ltd

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• At least 18 years of age.
• Signed informed consent.
• Untreated, histologically confirmed adenocarcinoma of the prostate.
• High-risk or greater PC defined by National Comprehensive Cancer Network Guidelines Version 1.202327 (clinical stage ≥T3a, or Grade Group ≥4, or PSA >20 ng/mL).
• Patients electing to undergo RP with PLND.

Exclusion Criteria:

• Administration of any high energy (>300 KeV) gamma-emitting radioisotope within 5 physical half-lives prior to Day 1.
• Known or expected hypersensitivity to 64Cu-SAR-bisPSMA or any of its components.
• Patients with known predominant small cell or neuroendocrine PC.

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Condition: Biochemically Recurrent Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04423211

Sponsor: ECOG-ACRIN Cancer Research Group

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION

Eligibility Criteria:

• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured creatinine clearance > 30 mL/min)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (1
• 5 or > 5 extra-pelvic lesions)

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Condition: Metastatic Castrate-sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05884398

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate
• Metastatic prostate cancer disease documented by conventional imaging (example, computed tomography [CT], magnetic resonance imaging [MRI], or bone scan) and/or next-generation imaging [NGI] demonstrating greater than equal (>=) 2 distinct extraprostatic sites of metastasis
• Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (example, wheelchair-bound due to prior spinal cord injury) and not related to prostate cancer or associated therapy
• A participant must agree not to plan to conceive a child while enrolled in this study or within 3 months after the last dose of study treatment
• Must be able to take whole apalutamide tablets by swallowing alone or with another vehicle (example, applesauce)
• Assigned male at birth, inclusive of all gender identities
• Participants who have undergone a bilateral orchidectomy and/or who are actively taking gender-affirming hormone therapy as part of their gender affirming care

Exclusion Criteria:

• History of seizure or known condition that has been determined to significantly predispose to seizure per investigator
• Pelvic lymph nodes as only site of metastasis
• Known allergies, hypersensitivity, or intolerance to excipients of apalutamide
• Any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events
• Gastrointestinal disorder affecting absorption

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Condition: Prostate Cancer, BRCA1 Mutation, BRCA2 Mutation, Prostatic Adenocarcinoma, High-Risk Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05498272

Sponsor: Rana McKay, MD

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Subject must meet all of the following applicable inclusion criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information prior to registration.
• Age ≥ 18 years at the time of consent.
• T stage 1-3 prostatic adenocarcinoma per AJCC staging manual Ed8.
• Histologically confirmed adenocarcinoma of the prostate without histological variants comprising >50% of the sample. Patients with intraductal carcinoma are eligible.
• Must have 3 core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within 7 months from registration. Less than 3 core biopsies are allowed if the patient has >1 cm or T3 disease on magnetic resonance imaging (MRI).
• Localized unfavorable intermediate or high-risk prostate cancer patients. Patients must have at least one of the following features:
• Gleason ≥ 4+3 (grade group 3, 4, 5) OR
• PSA > 20 ng/dL OR
• T3 disease NOTE: Patients with intraductal carcinoma are eligible independent of Gleason score, PSA and T stage.
• Must have evidence of germline or somatic BRCA1/2 gene alteration via standard of care CLIA based assay detection. Testing will be confirmed centrally but results of central testing not required for enrollment.
• No evidence of metastatic disease as determined by radionuclide bone scan and CT/MRI. Lymph nodes must be less than 20 mm in the short (transverse) axis.
• Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• White blood cell count ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Hemoglobin ≥ 10 g/dL with no transfusion support in the past 28 days
• Platelets ≥ 100,000/mcL
• Aspartate aminotransferase, alanine aminotransferase, and total bilirubin ≤ 1.5 x Institutional upper limit of normal
• Calculated creatinine clearance ≥ 51 mL/min based on Cockcroft-Gault formula or 24 hour urine. NOTE: See the protocol for Cockcroft-Gault formula or 24 hour urine.
• Life expectancy≥ 16 weeks.
• Subjects must use a condom plus spermicide beginning prior to treatment Cycle 1 Day 1, during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. See protocol for additional details.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

• Subjects meeting any of the criteria below may not participate in the study:
• Active infection requiring systemic therapy.
• Prior treatments not allowed: hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, apalutamide and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens and radiation therapy. Prior bicalutamide is allowed if taken for < 4 weeks prior to registration and there is a washout period of 2 weeks prior to the initiation of study treatment. LHRH agonist/antagonist therapy is allowed if begun within 4 weeks of registration. Prior 5-alpha reductase inhibitors are allowed but require a washout period of 2 weeks to initiation of study treatment.
• Prior treatment with a PARP inhibitor.
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
• tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice).
• Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Testing is not required unless there was a prior known positive hepatitis B or C test or hepatitis is suspected at screening. Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Known to have tested positive for human immunodeficiency virus (HIV) unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months.
• Severe hepatic impairment (Child-Pugh Class C).
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted.
• Active cardiac disease, defined as:
• Myocardial infarction within 6 months of study treatment.
• Uncontrolled angina within 3 months of study treatment.
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless an echocardiogram performed within 3 months of the screening visit results in a left ventricular ejection fraction that is ≥ 45%.
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
• Other clinically significant cardiovascular disease within 6 months of registration.
• Uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Individuals with a history of another malignancy are not eligible if the cancer is under active treatment or the cancer can be seen on radiology scans or if they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years.
• Major surgery within 4 weeks from start of treatment. Subjects must have recovered from any effects as the surgery as assessed by investigator discretion.
• Treatment with any investigational drug within 28 days prior to registration.
• Persistent toxicities Grade > 2 caused by previous cancer therapy (per Common Terminology Criteria for Adverse Event (CTCAE)).
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Patients considered a 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 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorders that prohibits obtaining informed consent.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
• Concomitant use of known strong CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to the protocol).
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.

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Condition: Cancer Of Prostate, Prostate Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04633252

Sponsor: National Cancer Institute (NCI)

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Participants must have documented histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• Participants must have metastatic disease, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.
• mCSPC participants:
• Participants must be within 134 days of starting ADT.
• If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases.
• For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease.
• For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis).
• mCRPC participants:
• Must need ADT as part of their cancer therapy (unless previous orchiectomy)
• Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
• Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC.
• Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan.
• Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to <= grade 1.
• Men age >=18 years. Because no dosing or adverse event data are currently available on the use of M9241 in combination with docetaxel in participants <18 years of age, children are excluded from this study.
• ECOG performance status 0-2.
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count >=1,500/mcL, without CSF support
• Platelets >=100,000/mcL
• Hemoglobin >9 g/dL
• PT <= 1.5 x ULN
• aPTT <= 1.5 x ULN
• Total bilirubin <= upper limit of normal (ULN), OR in participants with Gilbert s syndrome, a total bilirubin <= 3.0
• Serum albumin >=2.8 g/dL
• AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal -- Hepatic function based on Child-Pugh Class: Participants with hepatic impairment must have Child-Pugh Class A or better
• Serum Creatinine OR Creatinine Clearance <= 1.5 X institutional upper limits of normal OR >=50 mL/min/1.73 m^2 calculated by eGFR in the clinical lab for participants with serum creatinine levels > 1.5 ULN
• The effects of M9241 in combination with docetaxel and abiraterone on the developing human fetus are unknown. For this reason and because docetaxel agents as well as other immuno-therapeutic agents used in this trial are known to be teratogenic, sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom)after enrollment on study , during the study treatment and for 4 months after the last dose of abiraterone, docetaxel or M921, even if oral contraceptives are also used. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately and her partner should inform the study doctor immediately.
• Ability of subject to understand and the willingness to sign a written informed consent document. Subject should be willing to travel to the NIH for follow-up visits.
• Participants with prior immune checkpoint therapy are eligible to enroll upon PI discretion.

Exclusion Criteria:

• Immunocompromised status due to:
• Human immunodeficiency virus (HIV) positivity
• Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
• Other immunodeficiency diseases that in the opinion of the investigator could compromise the participants or limit treatment efficacy
• Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with a participant s ability to carry out the treatment program.
• Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
• Concurrent use of CYP3A4 inducers or sensitive CYP2D6 substrates within 14 days or 5 half-lives, whichever is shorter.
• Receipt of any investigational agent within 28 days (or 60 days for an antibody drug conjugates) before the first planned dose of study drugs.
• Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody
• Uncontrolled hypertension (SBP>170/ DBP>105)
• Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
• Participants who have had prior docetaxel for mCRPC
• mCSPC participants will be excluded if they did not start abiraterone within 6 weeks of ADT and/or had any docetaxel
• Participants who have had progression within 3 months of completing docetaxel for mCSPC
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to M9241 investigational agents used in the study
• The subject has had evidence within 3 years of the start of study treatment of another active malignancy which required systemic treatment (except for nonmelanoma skin cancers or carcinoma in situ of the bladder).
• The subject has active brain metastases or epidural disease.
• Participants with greater than or equal to grade 2 peripheral neuropathy (defined by CTCAE 5.0) at baseline.

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Condition: Castration-Sensitive Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05733351

Sponsor: Emory University

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Age >= 18 years
• Histologically confirmed adenocarcinoma of the prostate with metastatic disease
• Castration-sensitive status: either not have been treated with androgen deprivation therapy (ADT) (hormone therapy) or not on ADT at the time of progression
• Participants can have received up to 3 months of ADT with luteinizing hormone-releasing hormone (LHRH) agonists or antagonists or orchiectomy with or without concurrent first-generation antiandrogens prior to enrollment, with no radiographic evidence of disease progression or rising prostate-specific antigen (PSA) prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy > 12 weeks as determined by the investigator
• Hemoglobin >= 9.0 g/dl (within 28 days of cycle 1 day 1) (no transfusions allowed within 7 days of Cycle 1 Day 1 to meet entry criteria)
• White blood cell (WBC) >= 2000/uL (within 28 days of cycle 1 day 1) (after at least 7 days without growth factor support or transfusion)
• Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of cycle 1 day 1) (after at least 7 days without growth factor support or transfusion)
• Platelets >= 100,000/mcL (within 28 days of cycle 1 day 1) (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria)
• Prothrombin time (PT)/ partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 3 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
• Serum creatinine =< 2 mg/dL (or glomerular filtration rate >= 40 mL/min) (within 28 days of cycle 1 day 1)
• Willingness to provide pre- and post-treatment fresh tumor biopsies, if safe and medically feasible
• Male subjects must be surgically sterile or must agree to use adequate method of contraception from the time of consent until at least 120 days after the last dose of Xmab27017
• Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol specified laboratory tests, other study procedures, and study restrictions
• Completion of all previous surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy for the treatment of cancer >= 2 weeks before the start of study therapy. (No radiotherapy to Xmab27017 injection site within 4 weeks)
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1)
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
• Prior treatment with any CTLA4, PD1, or PDL1, or directed immunotherapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to (investigational new drug [IND] agent[s]) or other agents used in study
• Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), are clinically stable, and are without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
• Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
• Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted.)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receipt of an organ allograft
• Known history of left ventricular ejection fraction =< 40%
• Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted. COVID-19 vaccines are permitted)
• Known human immunodeficiency virus (HIV) positive subject with CD4+ T-cell (CD4+) counts < 350 cells/uL, or an HIV viral load greater than 400 copies/mL, or a history of an AIDS (acquired immunodeficiency syndrome)-defining opportunistic infection within the past 12 months, or who has not been on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.)
• Known positive test for hepatitis C ribonucleic acid (RNA) (a subject who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible).
• Known positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb; a subject whose HBsAg is negative and HBcAb is positive may be enrolled if a hepatitis B virus [HBV] deoxyribonucleic acid (DNA) test is negative, and the subject is retested for HBsAg and HBV DNA every 2 months)

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Condition: Prostatic Neoplasm

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05162573

Sponsor: The Netherlands Cancer Institute

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologically proven prostate cancer;
• cT2-4, partly determined by MRI;
• N1, determined by LND/SNP and/or PSMA PET/CT;
• iM0, determined by PSMA PET/CT;
• Accepted for curative intent treatment with EBRT of the prostate and regional nodes + 3y ADT;
• Visually PSMA-positive primary tumor and nodes, largest lesion ≥ average liver uptake;
• WHO performance score 0-1;
• Age > 18 years;
• For patients who have partners of childbearing potential: Willingness to use a method of birth control with adequate barrier protection during the study and for 6 months after the study drug administration; and
• Signed written informed consen

Exclusion Criteria:

• Inability to comply to study procedures;
• Inability to adhere to radiation safety measures in hospital or at home;
• Inability to undergo the required biodistribution scans;
• Prior or current malignant disease with potential impact on treatment outcome or survival;
• Prior treatment with EBRT;
• Prior treatment with ADT, already initiated >1 month before the start of EBRT;
• Prior treatment with radionuclide therapies, 177Lu-PSMA-617 or other;
• Reduced bone marrow reserve (Hb<6 mmol/L, Leukocytes<2.5 10E9/L, or Platelets<100 10E9/L not older than 1 month before start of EBRT);
• Reduced renal function (GFR < 60 not older than 1 month before start of EBRT);
• Reduced salivary gland function (history of prior salivary gland disease); or
• Miction problems requiring pre-treatment with ADT.

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04946370

Sponsor: Weill Medical College of Cornell University

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum 99 Years
• Gender: Male

Inclusion Criteria:

• Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate adenocarcinoma.
• A male participant must agree to use a contraception during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period.
• Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions
• ECOG performance status of 0-1
• Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
• Have previously been treated with at least one of the following in any disease state: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate). These drugs may have been initiated in the metastatic hormone sensitive or non-metastatic (M0) CRPC setting provided they meet criteria for progressive mCRPC at study entry.
• Age > 18 years
• Patients must have normal organ and marrow function as defined: Absolute neutrophil count >2,000 cells/mm3, Hemoglobin ≥9 g/dL, Platelet count >150 x 10^3/mcL, Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min/1.73 m2 by Cockcroft-Gault, Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT <3 x ULN in absence of liver metastases; < 5x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria), Serum internalized normalized ratio (INR) OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) must be <1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior receipt of chemotherapy for castration-resistant prostate cancer. Prior receipt of docetaxel chemotherapy in the hormone sensitive setting or for localized disease is acceptable provided at least 6 months has passed since the last dose.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Prior bone-seeking beta-emitting radioisotopes (e.g. Sm-153, Sr-89) or investigational PSMA-targeted therapy; prior radium-223 is allowed provided last dose administered >12 weeks prior to C1D1 on this study
• Has a history of a second malignancy, unless treatment with curative intent has been completed with no evidence of malignancy for 2 years. Patients with treated localized non-melanoma skin care, non-muscle invasive urothelial carcinoma, or carcinoma in-situ of other site are not excluded.
• Known history of myelodysplastic syndrome
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or <5 half-lives prior to enrollment.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Diagnosis of deep vein thrombosis and/or pulmonary embolus within 1 month of C1D1
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has received radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study. These drugs may be added after week 12.
• Unless azoospermia is present (whether due to surgery or underlying medical condition), having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principal investigator and chairperson during the study and for 4 months after last study drug administration.
• Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines are allowed.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy at the time of treatment initiation
• Has a known history of active TB (Bacillus Tuberculosis)
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has had an allogenic tissue/solid organ transplant

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Condition: Metastatic Castration-resistant Prostate Cancer, mCRPC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05340374

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Male patients aged 18 years or older at the time of informed consent.
2. Patient has provided written informed consent.
3. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Patients must have had prior treatment with docetaxel.
6. Patients must have progressed on a second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, or apalutamide) in the castrate-resistant setting.
7. Patients must have progressive disease. The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines this as any one of the following:
8. PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
9. Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
10. Bone progression: ≥ 2 new lesions on bone scan
11. At least three weeks since the completion of surgery prior to registration.
12. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
13. Serum testosterone levels ≤ 1.75nmol/L within 28 days prior to registration.
14. Imaging evidence of metastatic disease documented with either whole body bone scan (WBBS) or computed tomography (CT) scan performed within 28 days prior to registration.
15. Significant prostate-specific membrane antigen (PSMA) avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease.
16. Patients must have a life expectancy ≥ 12 weeks.
17. Assessed by a medical oncologist as suitable for treatment with cabazitaxel and 177Lu-PSMA-6
18. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
19. Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last 28 days prior to registration)
20. Absolute neutrophil count (ANC) ≥ 1.5x10^9/L
21. Platelets ≥ 150 x10^9/L
22. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
23. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
24. Albumin ≥ 25 g/L
25. Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft-Gault equation
26. Sexually active patients are willing to use medically acceptable forms of barrier contraception.
27. Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Exclusion Criteria:

1. Superscan on WBBS or diffuse marrow disease on PSMA PET.
2. Site(s) of measurable disease that are FDG-positive with low PSMA expression (SUVmax <10).
3. Prior treatment with cabazitaxel or 177Lu-PSMA-6
4. Contraindications to the use of corticosteroid treatment.
5. Other malignancies within the previous 2-years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
6. Presence of untreated brain metastases or leptomeningeal metastases.
7. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
8. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
9. Persistent toxicities (CTCAE v5.0 >/= Grade 2) caused by previous cancer therapy, excluding alopecia.
10. Known HIV or hepatitis B or C infection.
11. Radiotherapy or systemic anti-cancer therapies administered within 14 days prior to registration, excluding androgen deprivation therapy (ADT).

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Condition: Metastatic Castration-resistant Prostate Cancer, mCRPC, Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05383079

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patient must be ≥ 18 years of age and must have provided written informed consent.
• Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer. (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum PSA.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patients must have progressed on ≥ 1 second-generation AR-targeted agent (e.g., enzalutamide, abiraterone, apalutamide, or darolutamide).
• Patients must have progressive disease for study entry. PCWG3 defines this as any one of the following:
• PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.
• Soft tissue progression as per RECIST 1.1 criteria
• Bone progression: ≥ 2 new lesions on bone scan
• Symptomatic progression eg. Bone pain
• At least three weeks since receiving anti-cancer treatment (other than ADT), the completion of surgery or radiotherapy prior to registration.
• Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
• Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL) within 28 days before registration.
• Significant PSMA avidity on PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax >10 at sites of measurable disease >10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
• ≥ 2 bone metastases must be present on bone scintigraphy which have not been previously treated with radiotherapy.
• No contraindication to treatment with a bone antiresorptive agent such as denosumab or zoledronic acid.
• Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
• Haemoglobin ≥ 90 g/L independent of transfusions (no red blood cell transfusion in last four weeks)
• Absolute neutrophil count ≥ 1.5x10^9/L
• Platelets ≥ 150 x10^9/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component.
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases
• Albumin ≥ 25 g/L
• Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40 mL/min using the Cockcroft Gault equation
• Sexually active patients are willing to use medically acceptable forms of barrier contraception.
• Willing to undergo biopsies, if disease is considered accessible and biopsy is feasible.
• Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from study entry:
• Superscan on Bone scan (WBBS) or diffuse marrow involvement on PSMA PET/CT
• Prior treatment with 223Ra or 177Lu-PSMA.
• Has received more than one previous line of chemotherapy for the treatment of metastatic prostate cancer.
• Sites of discordant FDG-positive disease defined by minimal PSMA-expression and no uptake on WBBS (for bone metastases).
• Other malignancies within the previous 2 years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
• Symptomatic brain metastases or leptomeningeal metastases.
• Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ four weeks.
• Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.

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Condition: Biochemically Recurrent Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05526248

Sponsor: Bayer

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Male of ≥ 18 years of age.
• Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate.
• Prior treatment with primary radical prostatectomy or definitive RT for localized prostate cancer
• Patients must have PSA ≥0.2 ng/mL after ART or SRT post-RP or after RP in participants who are unfit for ART or SRT, OR PSA ≥2 ng/mL above the nadir after primary RT only. (RP, radical prostatectomy; ART, adjuvant radiotherapy; SRT, salvage radiotherapy; RT primary radiotherapy)
• The presence of < 5 asymptomatic metastatic lesions on conventional or PSMA-PET based imaging methods permitted. Lesions that need treatment with any opioid based analgetic are considered symptomatic
• PSADT ≤ 20 months calculated per PCWG3 + RECIST 1.1 per Scher et al. (Scher et al. 2016) and MSKCC nomogram.
• Eastern Cooperative Oncology Group ECOG (PS) of 0
• 1.
• Serum testosterone >150 ng/dl.
• Patients must have adequate organ function within 4 weeks before the first dose of study intervention.
• More than 30 days (or 5 half-lives) (whichever is longer) since prior participation in another clinical trial with an investigational medicinal product.

Exclusion Criteria:

• Prior treatment with ADT of up to 6 months for localized disease is permitted but not if during the prior 6 months before first dose of study intervention. Plan to initiate ADT during the trial period is not allowed.
• Radiation therapy or major surgery within 4 weeks of screening.
• Systemic glucocorticoids within 3 months prior to the first dose or study intervention was expected to require systemic glucocorticoids during the study period
• Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
• Uncontrolled hypertension
• A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study intervention.
• Prior history of a clinically significant malignancy with the exception of basal cell, squamous cell carcinoma of the skin, and superficial bladder cancer.
• Prior treatment with:
• Second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide other investigational AR inhibitors
• or Cytochrome P17 enzyme inhibitor such as abiraterone acetate as antineoplastic treatment for prostate cancer
• Prior history of gynecomastia
• Use of herbal products that may have had hormonal anti-prostate cancer activity or were known to decrease PSA levels (e.g., saw palmetto) within 4 weeks before the first dose of study intervention

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05075577

Sponsor: ESSA Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Males ≥18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone ≤1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
• Demonstrate adequate organ function.

Exclusion Criteria:

• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.

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