Prostate Cancer

Condition: Metastasis From Malignant Tumor of Prostate

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05204927

Sponsor: Curium US LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

1. Male 18 years or older able to understand and provide signed written informed consent.
2. Histologically or pathologically confirmed prostate adenocarcinoma without predominant small cell component.
3. Progressive disease by one or more of the following criteria:
4. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL.
5. Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria).
6. Previous treatment with next-generation androgen receptor (AR)-directed therapy (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).
7. Must have received no more than one previous AR-directed therapy.
8. Must have been administered ARAT (abiraterone, enzalutamide, darolutamide, or apalutamide) in the castration-sensitive or castration-resistant setting.
9. Must have progressed while on ARAT.
10. PSMA-PET scan (e.g., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by central reader.
11. Effective castration with serum testosterone level of <50 ng/dL and plan to continue with chronic medical or surgical castration.
12. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
13. Patients with HIV that are healthy and with a low risk of acquired immune deficiency syndrome related outcomes may participate in the trial at the investigators' discretion.
14. Patients with HBV and HCV may also participate if symptoms are sufficiently managed.
15. Life expectancy of at least 6 months as assessed by investigator.
16. Willing to initiate ARAT therapy determined by investigator.
17. For patients who have partners of childbearing potential: The patient and/or partner must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after the last study drug administration.

Exclusion Criteria:

1. Prior treatment with radioligand therapy including other lutetium-labeled compounds.
2. Prior treatment with radium-223 (Xofigo) within the past 12 weeks.
3. Prior chemotherapy treatment for castration-resistant prostate cancer. Prior docetaxel use in the hormone-sensitive setting is permitted, as long as no more than 6 doses were received, the last dose was administered >1 year prior to consent, and disease progression did not occur during docetaxel treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2
5. Patients with known HRR gene-mutation who have not been previously treated with olaparib or rucaparib.
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
7. Inadequate organ and bone marrow function as evidenced by:
8. Hemoglobin < 8 g/dL.
9. Absolute neutrophil count < 1.5 x 109/L.
10. Platelet count < 100 x 109/L.
11. AST/SGOT and/or ALT/SGPT > 3.0 x ULN.
12. Total bilirubin > 2 x ULN unless patient has known Gilbert's syndrome and then may be 3 x ULN.
13. Creatinine clearance (CrCl) < 50 mL/min based on the Cockcroft-Gault equation.
14. Albumin ≤ 2.75 g/dL
15. Patients who undergo a transfusion for the sole purpose of meeting eligibility for this trial will be excluded.
16. Assessment by the Investigator as unable or unwilling to comply with the requirements of the protocol.
17. Use of an investigational therapeutic drug within the last 4 weeks prior to start of study treatment or scheduled to receive one during the study period.
18. Known CNS metastasis unless received therapy, asymptomatic and neurologically stable.
19. Patients receiving zoledronic acid for bone-targeted therapy must be on stable dose for 4 weeks prior to randomization.
20. Major surgery within 30 days of randomization as determined by the Investigator.
21. Patients with active significant cardiac disease defined by any of the following:
22. New York Heart Association class 3 or 4 congestive heart failure within 6 months of signing the ICF unless treated with improvement.
23. Current diagnosis of electrocardiogram abnormalities with significant cardiac arrhythmias
24. History of long QT syndrome or know history of Torsades de Pointe
25. History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months of ICF signature
26. Participants with symptomatic cord compression or clinical/radiological findings indicating impending spinal cord compression
27. Patients with a superscan seen on baseline bone scan as determined by investigator.
28. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
29. Previous use of G-CSF for persistent neutropenia after standard of care treatment.
30. Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy.
31. Participants with active Covid
32. Recovered patients may be included when completely recovered (no symptoms at least 28 days before study medication and a negative Covid test within 72 hours).

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Condition: Metastasis From Malignant Tumor of Prostate (Disorder)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05653856

Sponsor: Curium US LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

1. Patients with histologically proven prostate adenocarcinoma.
2. Prior radical prostatectomy or radiation therapy with curative intent.
3. Recurrence of disease defined as:
4. Prior Radical Prostatectomy: PSA > 0.2 ng/mL, or
5. Prior Radiation Therapy: 2 ng/mL rise in PSA over post-treatment nadir
6. Patients with at least one extraprostatic site of disease suspected based on prior imaging or diagnosed by biopsy.
7. Age greater than or equal to 18 years.
8. Able to understand and provide signed written informed consent.

Exclusion Criteria:

1. Androgen deprivation therapy (ADT) or other therapies targeting the androgen pathway, unless subject has a rising PSA level.
2. Body weight greater than 350 lb (158 kg).
3. Investigational therapy within the past 30 days.
4. Creatinine clearance (ClCr) less than 30 mL/min.
5. Participants who are capable of fathering a child and who are unwilling to take precautions to prevent pregnancy.

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Condition: Prostatic Neoplasms, Neoplasm Metastasis, Urogenital Neoplasms, Physiological Effects of Drugs, Antineoplastic Agents, Antineoplastic Agents, Hormonal, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Abiraterone Acetate, Steroid Synthesis Inhibitors, Cytochrome P-450, Enzyme Inhibitors, Prednisone, Prednisolone, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05288166

Sponsor: Eli Lilly and Company

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Adenocarcinoma of the prostate (as the predominant histology)
• High-risk metastatic hormone-sensitive prostate cancer. High risk is defined as:
• Greater than or equal to (≥)4 bone metastases by bone scan and/or
• ≥1 visceral metastases by computed tomography or magnetic resonance imaging
• Must have initiated androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or bilateral orchiectomy prior to randomization. Up to 3 months of ADT prior to randomization is permitted with or without first-generation anti-androgen.
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Prior treatment with abemaciclib or any other cyclin dependent kinase 4 and 6 (CDK4 & 6) inhibitor
• Development of metastatic prostate cancer in the context of castrate levels of testosterone
• Received any prior systemic therapy for metastatic prostate cancer (including investigational agents), except for ADT and first-generation anti-androgen
• Clinically significant cardiovascular disease as evidenced by myocardial infarction, arterial thrombotic events, or severe/unstable angina in the past 6 months, or New York Heart Association Class II to IV heart failure
• History of syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin, or sudden cardiac arrest. Chronic and hemodynamically stable atrial arrhythmia well-controlled on medical therapy is permitted
• Uncontrolled hypertension
• Clinically active or chronic liver disease, moderate/severe hepatic impairment
• Known untreated central nervous system (CNS) metastasis. Participants with a history of treated brain metastases are eligible if stable for at least 8 weeks prior to randomization and off corticosteroid for at least 2 weeks prior to randomization

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Condition: Metastatic Malignant Neoplasm in the Bone, Prostate Adenocarcinoma, Stage III Prostate Cancer AJCC v8, Stage IIIA Prostate Cancer AJCC v8, Stage IIIB Prostate Cancer AJCC v8, Stage IIIC Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04513717

Sponsor: NRG Oncology

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION
• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration
• High-risk disease defined as having at least one or more of the following:
• PSA > 20 ng/mL prior to starting ADT Note: Patients receiving a 5-alpha reductase inhibitor (ex. finasteride) at the time of enrollment are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors and the medication should be discontinued prior to randomization but a washout period is not required.
• cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.])
• Gleason score of 8-10
• Node positive by conventional imaging with a short axis of at least 1.0 cm
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration;
• Bone imaging within 120 days prior to registration;
• Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative NaF PET/CT or negative Axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or NaF PET will still be eligible
• CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only
• Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by ≥10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure ≥ 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
• Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
• Platelet count ≥ -100 x 10^3/uL independent of transfusion and/or growth factors (within 120 days prior to registration)
• Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
• For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility
• Either a CrCl ≥ 30 ml/min or calculated glomerular filtration rate (GFR) ≥ 30 will make a patient eligible
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 120 days prior to registration)
• Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject is eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (within 120 days prior to registration)
• Serum albumin ≥ 3.0 g/dL (within 120 days prior to registration)
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with apalutamide
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• PRIOR TO STEP 2 RANDOMIZATION
• Confirmation of Decipher score
• 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 within 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
• For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization

Exclusion Criteria:

• PRIOR TO STEP 1 REGISTRATION:
• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI)
• Prior systemic chemotherapy within ≤ 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration
• Prior radical prostatectomy
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
• History of any of the following:
• Seizure disorder
• Current severe or unstable angina
• New York Heart Association Functional Classification III/IV (Note: 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.)
• History of any condition that in the opinion of the investigator, would preclude participation in this study
• Evidence of any of the following at registration:
• Active uncontrolled infection requiring IV antibiotics
• Baseline severe hepatic impairment (Child Pugh Class C)
• Inability to swallow oral pills
• Any current condition that in the opinion of the investigator, would preclude participation in this study
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is ≤ 60 days prior to registration; Please note: baseline PSA must be obtained prior to the start of any ADT
• PRIOR TO STEP 2 RANDOMIZATION:
• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration
• For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04886986

Sponsor: Weill Medical College of Cornell University

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• 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 0-2
• Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy
• Have previously been treated with at least one of the following: Androgen receptor signaling inhibitor (such as enzalutamide), CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician or refused taxane chemotherapy
• Age > 18 years
• Patients must have normal organ and marrow function as defined below: Absolute neutrophil count: >2,000 cells/mm3, Hemoglobin: ≥9 g/dL, Platelet count: >150,000 x 109/uL, Serum creatinine: <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 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: <1.5 x ULN in the absence of liver metastases; <3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
• Ability to understand, and the willingness to sign, a written informed consent document

Exclusion Criteria:

• Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1) or current enrollment in oncologic investigational drug or device study
• Use of investigational drugs ≤4 weeks or <5 half-lives of Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
• Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed provided at least 90 days have lapsed since last dose
• Prior PSMA-targeted radionuclide therapy (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides)
• Known active brain or leptomeningeal metastases
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of Treatment visit #1
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Radiation therapy for treatment of PC ≤4 weeks of Treatment visit #1
• 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
• Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for at least 140 days after last study drug administration
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse
• Known history of myelodysplastic syndrome

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Condition: Prostate Cancer, Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03763253

Sponsor: Imperial College London

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

1. Diagnosed with prostate cancer within 6 months of screening visit
2. Metastatic disease (Any T, Any N, M1+) of any grade, stage or Prostate Specific Antigen (PSA) level.
3. Fit to undergo standard of care treatment for metastatic disease and both minimally invasive therapy and prostate radiotherapy/prostatectomy.
4. Performance status 0-2
5. Histologically proven local tumour

Exclusion Criteria:

1. Patient did not undergo and/or is unable to undergo standard of care baseline imaging tests for confirmation of metastatic status (CT abdomen/pelvis AND chest Xray (or CT chest) AND radioisotope bone scan (or whole body imaging such as MRI or PET imaging as alternative to all preceding scans mentioned here) AND prostate MRI.
2. Prior exposure to long-term androgen deprivation therapy or hormonal therapy for the treatment of prostate cancer unless started within 4 months of screening visit.
3. Prior chemotherapy or local or systemic therapy for treatment of prostate cancer (apart from ADT or hormonal therapy as outlined above)

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Condition: Prostate Cancer, Stage IV Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05189457

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Biopsy proven prostate cancer and the diagnosis can be established through either prostate biopsy or biopsy of a metastatic lesion. High risk mCSPC is defined as having 2 of the 3 risk factors: a Gleason score of 8 or more, at least 3 bone metastases, and the presence of measurable visceral metastasis.
• ECOG performance status of 0-1
• No androgen deprivation therapy (ADT) with LHRH analogue monotherapy for more than 12 weeks after the diagnosis of metastatic prostate cancer. Prior ADT in the non-metastatic setting is allowed if it was given > 2 years prior to the diagnosis of metastatic prostate cancer and a reduction of PSA is documented after initiating ADT in the metastatic setting.
• Agreeable to prostate biopsy after completing "second strike".
• Adequate organ function with absolute neutrophil count > 1000/l, Hb > 10 g/dl, Platelet > 100,000/l, Creatinine and liver enzymes within 1.5 folds of upper limits of normal
• No uncontrolled arrhythmia; participants with h/o myocardial infarction or history of congestive heart failure, need to have estimated left ventricle ejection fraction above 40% either on echocardiogram or MUGA scan within 6 months of study enrollment.
• All men who are sexually active with a female partner of childbearing potential treated or enrolled on this protocol must agree to use highly effective barrier contraception prior to the study, for the duration of study participation, and for 7 months after last dose of tislelizumab administration.
• Ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the participants behalf. Stated willingness to comply with all study procedures and availability for the duration of the study
• Inclusion of minorities: Men of all races and ethnic groups who met the above inclusion criteria are eligible for this trial. Exclusion Criteria:
• Prior treatments with TAK-700/Orteronel, abiraterone, darolutamide, apalutamide or enzalutamide for more than eight weeks.
• Any previous treatment with a PD-1 or PD-L1 inhibitor
• Documented brain metastases
• Prior prostatectomy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel (including any drugs formulated with polysorbate 80), or LHRH analogue (e.g., leuprolide, triptorelin, goserelin acetate, degarelix)
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy & have any evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• 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
• Participants with delayed healing of wounds, ulcers, and/or bone fractures
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for tislelizumab to be less clinically active in this population.
• Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, with the following exceptions: • Vitiligo or alopecia • Hypothyroidism stable on hormone replacement • Chronic skin condition that does not require systemic therapy • Celiac disease controlled by diet alone • Participants with inactive disease in the last 5 years may be included.
• Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants with positive HCV antibody are eligible if polymerase chain reaction is negative for HCV RNA.
• Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study chemoimmunotherapy, with the following exceptions: premedication for docetaxel with 8 mg oral dexamethasone approximately 12 hr, 8 hr and 1 hr prior to each docetaxel administration; intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection); systemic corticosteroids at physiologic doses not exceeding 10mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before CT scan)
• History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
• Was administered a live vaccine ≤ 4 weeks before first dose of tislelizumab NOTE:Seasonal vaccines for influenza and COVID-19 vaccines are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Inability to comply with protocol requirements
• Inclusion of minorities: Men of all races and ethnic groups who met the above

Exclusion Criteria:

• Prior treatments with TAK-700/Orteronel, abiraterone, darolutamide, apalutamide or enzalutamide for more than eight weeks.
• Any previous treatment with a PD-1 or PD-L1 inhibitor
• Documented brain metastases
• Prior prostatectomy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel (including any drugs formulated with polysorbate 80), or LHRH analogue (e.g., leuprolide, triptorelin, goserelin acetate, degarelix)
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy & have any evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• 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
• Participants with delayed healing of wounds, ulcers, and/or bone fractures
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for tislelizumab to be less clinically active in this population.
• Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, with the following exceptions: • Vitiligo or alopecia • Hypothyroidism stable on hormone replacement • Chronic skin condition that does not require systemic therapy • Celiac disease controlled by diet alone • Participants with inactive disease in the last 5 years may be included.
• Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants with positive HCV antibody are eligible if polymerase chain reaction is negative for HCV RNA.
• Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study chemoimmunotherapy, with the following exceptions: premedication for docetaxel with 8 mg oral dexamethasone approximately 12 hr, 8 hr and 1 hr prior to each docetaxel administration; intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection); systemic corticosteroids at physiologic doses not exceeding 10mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before CT scan)
• History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
• Was administered a live vaccine ≤ 4 weeks before first dose of tislelizumab NOTE:Seasonal vaccines for influenza and COVID-19 vaccines are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Inability to comply with protocol requirements
• Inclusion of minorities: Men of all races and ethnic groups who met the above exclusion criteria are eligible for this trial.

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Condition: Metastatic Castration-resistant Prostate Cancer, Androgen Resistant Prostatic Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04844749

Sponsor: Veru Inc.

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum 100 Years
• Gender: Male

Inclusion Criteria:

• Provide informed consent.
• Be able to communicate effectively with the study personnel.
• Aged ≥18 years.
• Histological or cytologic proof of adenocarcinoma of the prostate not including the diagnosis of small cell carcinoma of the prostate of neuroendocrine pathology.
• Radiographic evidence of metastatic disease at baseline by CT scan, or MRI and bone scan, with confirmation of measurable disease by RECIST 1.1 and/or identifiable discrete bone metastases by PCWG3.
• Known castration resistant prostate cancer, defined according to PCWG3 criteria.
• Have received at least one androgen receptor targeting agent (e.g. abiraterone, enzalutamide, darolutamide, or apalutamide).
• Subjects who have metastatic castration resistant prostate cancer that have maintained or have previously been treated with ADT (while on-study, patients must receive continuous ADT. Either chemical or surgical castration by bilateral orchiectomy is acceptable) and have failed prior treatment with at least one androgen receptor targeting agent (e.g. abiraterone, enzalutamide, darolutamide, or apalutamide) defined as:
• Serum PSA progression of two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 2 weeks apart. Or
• Documented bone lesions by the appearance of two or more new lesions on bone scintigraphy or bi-dimensionally-measurable soft tissue metastatic lesion assessed by CT or MRI.
• Treatment with an alternative androgen receptor targeting agent is a reasonable next line of therapy.
• Absolute PSA ≥2.0 ng/ml at screening.
• ECOG performance status <2.
• Participants must have normal organ and bone marrow function measured within 30 days prior to administration of study treatment as defined below:
• Hemoglobin ≥9.0 g/dL with no blood transfusion in the past 30 days
• Creatinine clearance ≥60 mL/min (using Cockcroft-Gault equation)
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Platelet count ≥100 x 109/L
• Total bilirubin ≤ upper limit of normal (ULN) (or <2.5 x ULN for patients with known Gilberts disease)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT))/Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤2.5 x ULN. NOTE: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded. Patients with chronic renal stent and stable creatinine elevation can be included in the study with written documentation from the PI.
• Participants must have a life expectancy >3 months.
• Subjects must agree to use acceptable methods of contraception:
• If the study subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e.,barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository).
• If female partner of a study subject has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository)should also be used.-If female partner of a study subject has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS),a barrier method (condom with spermicidal foam/gel/film/cream/suppository)should also be used.
• Other than metastatic prostate cancer, no evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin or other cancers treated with curative intent >3 years prior).
• Participants must agree to refrain from prolonged exposure to the sun or agree to use at least SPF 50 on all exposed skin and protective clothing during prolonged sun exposure throughout participation in this study and/or treatment with VERU- 111.
• Subject is willing to comply with the requirements of the protocol through the end of the study.

Exclusion Criteria:

• Known hypersensitivity or allergy to colchicine.
• Histologic identification of small cell carcinoma of the prostate or neuroendocrine pathology in either biopsy or prostatectomy tissue.
• A bone scan with evidence of superscan or superscan phenomenon, defined as:
• Uptake throughout the axial skeleton and proximal appendicular skeleton, often somewhat heterogeneous, or,
• Symmetrically intense and diffuse radiotracer uptake in the skeleton with absent or diminished visualization of the genitourinary system and soft tissues, or,
• Defined in the bone scan report as a superscan or superscan phenomenon. NOTE: Medical Monitor should be consulted prior to screening of a patient if a superscan or superscan phenomenon is suspected or possible, but undetermined by any of the above definitions.
• Has received external-beam radiotherapy within the last 2 weeks prior to start of study treatment.
• Patients with a QT interval corrected by Fridericia's formula of >480 ms.
• Patients receiving full dose warfarin therapy are not eligible for study.
• Patients with prior history of a thromboembolic event within the last 6 months.
• Participation in another clinical study with an investigational product during the last 6 months prior to randomization into this study.
• Patients should be excluded if they have had prior systemic treatment with prior taxane chemotherapies (for greater than 2 cycles) for advanced prostate cancer. Patient can have up to 2 cycles of prior taxane chemotherapy greater than one year prior to randomization and remain eligible for inclusion in this study. Taxane exposure in the adjuvant or neoadjuvant setting is allowed (maximum of 6 cycles).
• Any treatment modalities involving major surgery within 4weeks prior to the start of study treatment.
• Patients are excluded if they have known brain metastases or leptomeningeal metastases.
• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• 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. Active infections discovered during screening period must be treated and controlled before patient is dosed with VERU-111.
• Persistent toxicities (>Common Terminology Criteria for Adverse Event (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 6 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
• Total bilirubin levels > 1.5 x ULN (>2.5 x ULN in patients with known Gilbert's disease).
• AST and/or ALT levels >2.5xULN or AST and/or ALT levels >1.5xULN WITH concomitant alkaline phosphatase levels >2.5xULN.

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Condition: Prostate Cancer, Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04751929

Sponsor: Dana-Farber Cancer Institute

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Diagnosis of metastatic castration resistant prostate cancer (mCRPC), with histologic confirmation of adenocarcinoma of the prostate (without evidence of small cell carcinoma), with progressive disease at the time of study entry by either
• Sequence of at least 2 rising PSA values at a minimum of 1-week intervals
• Radiographic progression per RECIST1.1 for soft tissue and/or per PCWG3 for bone, with or without PSA progression
• Adult males 18 years of age or older.
• ECOG performance status of 0 or 1
• Patients must have metastatic disease by bone scintigraphy or other nodal or visceral lesions on CT or MRI with a bone or soft tissue lesion amenable to image-guided percutaneous biopsy, and the patient must be evaluable for disease response by either
• Baseline PSA ≥ 2.0 ng/mL OR
• Measurable disease per RECIST 1.1
• Past progression or intolerance to at least one novel antiandrogen therapy (abiraterone, enzalutamide, galeterone, apalutamide, darolutamide, orteronel, seviteronel or equivalent) in either the hormone-sensitive or castration-resistant disease setting.
• Not a candidate for docetaxel or cabazitaxel chemotherapy due to:
• progression within 12 months of completion or intolerance to prior taxane OR
• refusal of taxane OR
• contraindication to, or lack of fitness for taxane OR
• Investigator assessment that taxane is not clinically indicated or preferred.
• Maintenance of castration status, defined as serum testosterone level of less than 50 ng/dL. Patients must be surgically castrate or maintained on LHRH agonist or antagonist therapy for the duration of the study period.
• Must have recovered from any treatment-related toxicities to ≤ CTCAE grade 1.
• Patients with ≤ CTCAE grade 2 anorexia, alopecia, neuropathy, and/or fatigue however, are also permitted to enroll.
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• hemoglobin ≥9 g/dL (without transfusion or growth factor in prior 28 days)
• platelets ≥100,000/mcL (without transfusion or growth factor in prior 28 days)
• total bilirubin ≤1.5 × institutional upper limit of normal, unless the subject has known or suspected Gilbert's syndrome
• AST(SGOT)/ALT(SGPT) ≤1.5 × institutional upper limit of normal
• creatinine clearance ≥30 mL/min/1.73 m2
• Life expectancy of at least 6 months, as determined by a study Investigator.
• Ability to swallow oral medications.
• Ability to understand and willingness to sign an IRB-approved informed consent.
• Additional Inclusion Criteria (Arm C patients)
• Must have documentation (via CLIA approved, CAP certified next generation sequencing [NGS] assay report) of genomic aberration resulting in CDK12 loss of function in metastatic tumor tissue.
• Patients whose tumors have not previously undergone NGS are not eligible for Arm C but are eligible for the randomized unselected cohorts.

Exclusion Criteria:

• Clinical evidence of, or known and untreated metastatic CNS disease.
• Concurrent active malignancy.
• Patients with non-melanomatous skin cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject to be in remission, or any prior malignancy that was treated with curative intent (no evidence of disease for at least 3 years) are also permitted to enroll.
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
• Patients who have received oral anti-neoplastic intervention such as an oral hormonal agent, PARP inhibitor, AR targeted therapy, or oral experimental agent within 14 days prior to planned cycle 1 day 1 of study treatment.
• Prior treatment with an inhibitor of CDK4 and/or 6.
• Prior treatment with an inhibitor of PD-1, PD-L1, or PD-L2.
• Patients on concurrent therapy with a moderate or strong CYP3A4 inducer or inhibitor which cannot be safely stopped at least five half-lives prior to initiation of therapy with abemaciclib.
• Evidence of an active autoimmune disease that has required systemic treatment within the last 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Patients with conditions requiring replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are permitted to enroll.
• Live vaccine within 30 days of registration.
• Active smoking or a history of smoking greater than 20 pack-years (i.e. # packs of cigarettes smoked per day × # of years patient has smoked > 20).
• Prior history of radiation therapy to thorax (including to lungs/pleura, esophagus, intrathoracic lymph nodes, C7-L2 vertebrae, or ribs) for any reason and any duration/dose.
• Any history of interstitial lung disease, pneumonitis or idiopathic pulmonary fibrosis, regardless of remission or immunosuppression status.
• Any history of lung cancer, regardless of stage or treatment
• Any of the following abnormalities on pre-treatment pulmonary function testing:
• FEV1/FVC < lower limit of normal (LLN) and FEV1 < 75% predicted OR
• FVC < 70% of predicted, regardless of FEV1/FVC ratio OR
• DLCO (corrected for hemoglobin) < 70% of predicted
• Active bacterial or fungal infection, or known detectable viral infection (e.g., Human Immunodeficiency Virus [HIV] or viral hepatitis).
• Arterial or venous thromboembolic event within the last 3 months.
• Significant infection, medical condition, or social situation which, in the opinion of the investigator, would preclude participation or limit the patient's ability to comply with study requirements.

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Condition: Metastatic Hormone-sensitive Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05059236

Sponsor: Bayer

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of prostate. Participants may have begun androgen-deprivation therapy (up to 120 days prior to enrollment). Note: Relugolix is not permitted as ADT in this study.
• Metastatic disease and will be stratified by presence of high volume or low volume disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
• Adequate bone marrow, liver and renal function within 4 weeks of enrollment
• At least 4 weeks since prior major surgery and recovered from all toxicity from such surgery prior to enrollment
• Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following criteria are met:
• Therapy was discontinued ≥ 12 months ago AND there was a clinical state without evidence of disease at least 12 months after completing adjuvant or neoadjuvant hormonal therapy, as defined by 1 of the following:
• PSA < 0.1 ng/mL after prostatectomy plus hormonal therapy
• PSA < 0.5 ng/mL and has not doubled above nadir after radiotherapy plus hormonal therapy
• Therapy lasted no more than 24 months
• Prior palliative radiotherapy allowed for participants, if commenced within 30 days before starting androgen deprivation.
• Bicalutamide, nilutamide or flutamide are allowed as single-agent therapy ≤ 28 days before medical castration to prevent flare.

Exclusion Criteria:

• PSA met criteria for PSA progression
• History of malignancy in the past 5 years, with the exception of basal cell and squamous cell carcinoma of the skin.
• Had any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, congestive heart failure, hospitalization for any cardiac event, including conduction abnormalities
• Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate
• Known brain/ leptomeningeal metastases
• An active viral hepatitis (defined as Hepatitis B surface antigen [HBsAg] reactive or detectable [qualitative] HBV DNA defined as HCV Ribonucleic Acid [RNA] [qualitative] is detected), known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment
• Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
• A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
• Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the participant and/or his compliance with study procedures or may interfere with the participant's participation in the study or evaluation of the study results.
• Prior hormone therapy in the metastatic setting
• Prior chemotherapy in the adjuvant or neoadjuvant setting
• Concurrent use or previous exposure of 5-alpha reductase inhibitors (within 28 days before the start of darolutamide or 5 half-lives of the drug, whichever is longer)
• Any Prior treatment with second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, or other investigational AR inhibitors, Cytochrome P17 enzyme inhibitor such as abiraterone acetate or other investigational CYP 17 as antineoplastic treatment for prostate cancer
• Previous (within 28 days before the start of darolutamide or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
• Contraindication to both CT and MRI contrast agent
• Hypersensitivity to any of the study treatments, study treatment classes, or excipients in the formulation of the study treatments
• Inability to swallow oral medications

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Condition: Metastatic Castration-Resistant Prostate Cancer, Metastatic Castration-Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04666129

Sponsor: Myovant Sciences GmbH

Phase: Phase 1

Eligibility:

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

Key Inclusion Criteria:

• 1. A diagnosis of adenocarcinoma of the prostate confirmed by histologic or cytologic evidence and with a documented medical history of either:
• mCSPC (Parts 1, 2, and 3) defined as having at least two of three risk factors at the baseline (Day 1) visit:
• Total Gleason score of ≥ 6; and
• Presence of ≥ 2 metastatic lesions on bone scan; OR
• Radiologic evidence of measurable visceral metastases with exception of hepatic metastases.
• nmCRPC (Part 2 only) defined as disease progression despite maintaining castration levels of testosterone with androgen deprivation therapy (ADT), as evidenced by an increase in consecutive prostate-specific antigen (PSA) concentrations (2 measurements, at least one week apart).
• mCRPC (Parts 1 and 3) defined as disease progression despite maintaining castration levels of testosterone with ADT:
• An increase in consecutive PSA (2 measurements at least 1 weeks apart);
• Worsening clinical symptoms;
• Radiologic evidence demonstrating enlarged metastatic lesions or the development of new metastases. 2. Currently receiving standard-of-care treatment of leuprolide acetate (3-, 4-, or 6-month injections [intramuscular Lupron or subcutaneous Eligard]) or a gonadotropin-releasing hormone (GnRH) receptor antagonist (such as degarelix) in combination with:
• Part 1: abiraterone acetate 1000 mg or fine-particle abiraterone acetate 500 mg once daily plus prednisone 5 mg once daily for participants with mCSPC or twice daily for participants with mCRPC or methylprednisolone 4 mg once daily and in whom abiraterone has been well tolerated (that is, without evidence of hepatotoxicity requiring dose adjustment for abiraterone).
• Part 2: apalutamide 240 mg once daily and in whom apalutamide has been well tolerated (that is, without a fracture, fall, or seizure episode or need to dose adjust due to any adverse events).
• Part 3: docetaxel 75 mg/m2 and in whom docetaxel has been well tolerated (that is, no evidence of hypersensitivity reaction, febrile neutropenia or neutrophils < 500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or moderate neurosensory signs and/or symptoms despite dose reduction).

Key Exclusion Criteria:

• A patient will not be eligible for inclusion in the study if any of the following criteria apply: 1. A medical history of brain or hepatic metastases based on radiologic evidence or a medical history of surgical castration; 2. Received combination treatment with a GnRH analog or GnRH receptor antagonist with either abiraterone acetate plus a corticosteroid (Part 1) or apalutamide (Part 2) in patients with mCSPC (Part 1 and Part 2) or nmCRPC (Part 2) for a total duration > 24 months or in patients with mCRPC (Part 1) for a total duration > 6 months; 3. Is scheduled or anticipates being scheduled for major surgery during the study treatment period; 4. A current diagnosis of a malignancy other than prostate cancer, with the exception of any of the following:
• Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of any type;
• Adequately treated Stage I cancer that is currently in remission and has been in remission for ≥ 2 years;
• Any other cancer from which the patient has been disease-free for ≥ 3 years; 5. Abnormal clinical laboratory test value(s) at the screening visit or prior to the baseline (Day 1) visit including:
• Serum creatinine > 2.0 mg/dL;
• Platelets < 100 × 103/μL;
• Hemoglobin < 10.0 g/dL;
• Leukocytes (WBC) < 3 × 103/μL;
• Absolute neutrophil count < 1.5 × 103/μL;
• Hemoglobin A1c (HbA1c) > 8%; Note (Part 3 only): Transfusions and/or administration of growth factors are permitted as indicated for the clinical management of docetaxel-related hematologic effects and in accordance with the investigator's judgement. 6. Known hepatic disease, including alcoholic liver disease or viral hepatitis such as hepatitis A (hepatitis A virus IgM positive), chronic hepatitis B (HbsAg positive), or chronic hepatitis C (HCV antibody positive, confirmed by HCV RNA) or clinical signs of hepatic disease such as jaundice; 7. A medical history within 6 months prior to the screening visit or a current diagnosis of any of the following:
• Myocardial infarction;
• Unstable angina;
• Unstable symptomatic ischemic heart disease;
• Congestive heart failure classified as NYHA class III or IV heart failure;
• Thromboembolic event(s) (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular event[s]);
• Any other significant cardiac condition (eg, pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease); 8. An abnormal ECG 9. Uncontrolled hypertension 10. Hypotension 11. Bradycardia 12. Positive HIV 13. Medical history of a bleeding disorder or current clinical evidence of gastrointestinal bleeding or active bleeding from another anatomical location. 14. A medical history within 1 year of the screening visit of drug or alcohol abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders V 15. Received an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to the baseline (Day 1) visit; 16. Prior use of any prohibited medication(s) and restrictive medication(s) without the appropriate washout period or use of a prohibited medication during the study treatment period is planned; 17. A contraindication or known history of hypersensitivity to any of the study treatments or components thereof, or has a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates study participation; 18. Any other medical or psychiatric condition that, in the opinion of the investigator, would interfere with accomplishing the study objectives or the patient completing the study; 19. Is a study site employee or is a primary family member (spouse, parent, child, or sibling) of a site employee involved in the conduct of the study.

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03637543

Sponsor: Beth Israel Deaconess Medical Center

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Patients must have signed an informed-consent form indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
• Patients must have a history of prostate adenocarcinoma (adenocarcinoma must be the primary histology; secondary components of variant histologies are acceptable) confirmed on biopsy and treated with primary radical prostatectomy (RP) or definitive radiation (RT). Prior salvage RT is acceptable.
• Patients must have experienced biochemical recurrence (BCR) plus have minimum PSA values noted below:
• Following primary RP: Any detectable rising PSA after RP (or after salvage RT if performed), minimum PSA 1.0 at time of screening
• Following primary RT: PSA rise to ≥2 ng/mL above the nadir
• No evidence of metastases on conventional imaging (CT or MRI plus bone scan)
• PSA doubling time (PSADT) <10 months --PSADT: calculated as per Prostate Cancer Working Group 3 (PCWG3) and the Memorial Sloan Kettering Cancer Center calculator: (https://www.mskcc.org/nomograms/prostate/psa_doubling_time) With linear regression model of normal logarithm of PSA and time, based on:
• At least 3 consecutive PSA values with each value ≥0.2 ng/mL
• Interval between first and last PSA values is ≥8 weeks but ≤12 months. -Archival tissue is mandatory, either prostatectomy specimen or (in patients who received primary RT) diagnostic core biopsies. Patients must consent to next-generation sequencing performed on this tissue.
• If diagnostic core biopsies are only available tissue, at least 3 cores must be involved by tumor
• Easteron Cooperative Oncology Group (ECOG) performance status 0-1
• Age ≥18 years
• Adequate organ and marrow function:
• System Laboratory Value
• Hematological
• White blood cell (WBC) ≥ 2000/µL
• Absolute Neutrophil Count (ANC) ≥ 1500/μL
• Platelets (Plt) ≥ 100 x103/μL
• Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion) -Renal
• Serum Creatinine ≤ 2 x ULN
• Hepatic
• Bilirubin1 ≤ 1.5× upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL
• Baseline testosterone ≥100 ng/dL
• Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no treatment-related toxicity ≥ grade 2.
• History of prior malignancy or concurrent separate malignancy is not an exclusion criterion so long as the non-prostate malignancy is stable and does not require any treatment.
• Able to understand and sign informed consent and adhere to study procedures.
• Male patients whose female partners are of reproductive potential must agree to use a contraception during the trial period

Exclusion Criteria:

• Current use of ADT or plan to initiate ADT during trial period
• Major surgery or radiation therapy within 14 days of starting study treatment
• Subjects with active autoimmune disease. Patients with a history of autoimmune disease that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system, heart, lungs, kidneys, skin, and gastrointestinal tract will be allowed.
• Known history of immune deficiencies or chronic viral infections including HIV, hepatitis B (HBV), and hepatitis C (HCV) (patients with prior therapy for HBV or HCV is permitted if viral clearance was documented).
• Concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day or equivalent. Use of inhaled, nasal, and topical steroids (applied to small body areas) is allowed.
• Current use (within past 4 weeks) of other prohibited medications including anti-cancer therapies, hormonal therapies, 5-alpha reductase inhibitors, and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
• Prior treatment with immune checkpoint inhibitors. (Prior cancer vaccines are allowed.)
• Serious intercurrent medical or psychiatric illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program

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Condition: Prostate Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03857477

Sponsor: Institute of Cancer Research, United Kingdom

Phase:

Eligibility:

• Age: minimum 55 Years maximum 69 Years
• Gender: Male

Inclusion Criteria:

• Men aged 55 to 69 years.
• Caucasian ethnicity.
• WHO performance status 0-2.
• Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

Exclusion Criteria:

• Non-Caucasian ethnicity (including mixed race or Ashkenazi Jewish (excluded as these groups have different genetic risk profiles from those being studied).
• Previous diagnosis of cancer with a life-expectancy of less than five years.
• Negative prostate biopsy within one year before recruitment.
• Previous diagnosis of prostate cancer.
• Co-morbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC medications (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy).
• Men with body mass index (BMI) 40 and above.
• Men with BMI 35 and above plus other co-morbidities.
• Contraindications to having an MRI (pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia).
• Any significant psychological conditions that may be worsened or exacerbated by participation in the study.

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Condition: Prostate Cancer, Artificial Intelligence, Radiotherapy

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04441775

Sponsor: Dartmouth-Hitchcock Medical Center

Phase:

Eligibility:

• Age: minimum 21 Years maximum 90 Years
• Gender: Male

Inclusion Criteria:

• Favorable-risk inclusion criteria (as per RTOG 0415) 1. Histologically confirmed prostate adenocarcinoma 2. Gleason Score <= 3+4 = 7 ( with less than 50% of all cores positive, and no more than one core with Gleason 3+4=7) 3. Clinical stage T1-T2b 4. Prostate Specific Antigen (PSA) <10 ng/ml within 180 days prior to treatment planning. PSA may not have been acquired within 30 days of stopping finasteride, or within 90 days of stopping dutasteride 5. RT treatment initiated between 1/1/15 and 12/31/16 6. Prostate MRI used as part of RT treatment planning 7. No previous hormonal therapy, such as LHRH agonists, estrogens, anti-androgens, or surgical castration 8. No previous use of finasteride within 30 days prior to planning 9. No previous use of dutasteride within 90 days prior to planning
• High-risk inclusion criteria (as per RTOG 0521) 1. Histologically confirmed prostate adenocarcinoma 2. PSA < 150 3. One of the following combinations: 1. Gleason 7 or 8 and PSA >= 20 2. Gleason 8 and clinical T-stage > T2a 3. Gleason 9 or 10 4. Negative bone scan within 180 days of planning 5. XRT treatment initiated between 1/1/15 and 12/31/16 6. Prostate MRI used as part of RT treatment planning 7. No previous hormonal therapy, such as LHRH agonists, estrogens, anti-androgens, or surgical castration, prior to prostate cancer diagnosis
• Intermediate-risk inclusion criteria 1. Histologically confirmed prostate adenocarcinoma 2. PSA < 20 3. Gleason 7 or 8 4. Not meeting criteria for favorable- or high-risk disease, as per above 5. XRT treatment initiated between 1/1/15 and 12/31/16 6. Prostate MRI used as part of RT treatment planning 7. No previous hormonal therapy, such as LHRH agonists, estrogens, anti-androgens, or surgical castration, prior to prostate cancer diagnosis

Exclusion Criteria:

1. Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease free for a minimum of 5 years
2. Evidence of distant metastases
3. Regional lymph node involvement
4. Previous radical prostate surgery or cryosurgery
5. Previous pelvic irradiation or prostate brachytherapy
6. Previous or concurrent cytotoxic chemotherapy for prostate cancer
7. Severe, active comorbidity, defined as follows:
8. Unstable angina, congestive heart failure, and/or transmural myocardial infarction requiring hospitalization within the last 6 months
9. Acute bacterial or fungal infection requiring intravenous antibiotics
10. Hepatic insufficiency resulting in clinical jaundice or coagulopathy
11. Acquired immune deficiency syndrome based upon current CDC-defined criteria
12. Zubrod performance status 2 or worse
13. Previous use of finasteride within 60 days of planning
14. Previous use of dutasteride within 180 days of planning

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04556916

Sponsor: University Hospital, Montpellier

Eligibility:

• Age: minimum 40 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patient :
• Men over 40 being suspicious of prostate cancer
• Subject with PSA ≥ 4 and designated for biopsy
• Subjects must be able to attend all scheduled visits and to comply with all trial procedures
• mpMRI done before prostate biopsy
• Subject must be covered by public health insurance
• Signed informed consent form Inclusion Criteria Subject Control Patient patient free from prostatic disease :
• Men over 40 with no suspicion of prostate cancer
• Subject with PSA < 2.5 and normal digital rectal examination
• Subject must be covered by public health insurance
• Signed informed consent form Exclusion Criteria Patient :
• Subject with histologically confirmed prostate cancer
• Subject with a verified viral infection (HIV or Hepatitis)
• Subject under Finasteride treatment
• Subject under hormonal treatment (analogs, antagonists, androgenics)
• Subject with other cancer diagnosed
• Subject unable to sign consent
• Planned longer stay outside the region that prevents compliance with the visit plan
• Subject deprived of liberty, protected adults or vulnerable persons
• Urinary infection ≤ 2 months
• Subject excluding health insurance registration
• Subject refusing to perform prostate biopsy
• Subject who are in a dependency or employment with the sponsor or the investigator

Exclusion Criteria:

• Patient :
• Subject with histologically confirmed prostate cancer
• Subject with a verified viral infection (HIV or Hepatitis)
• Subject under Finasteride treatment
• Subject under hormonal treatment (analogs, antagonists, androgenics)
• Subject with other cancer diagnosed
• Subject unable to sign consent
• Planned longer stay outside the region that prevents compliance with the visit plan
• Subject deprived of liberty, protected adults or vulnerable persons
• Urinary infection ≤ 2 months
• Subject excluding health insurance registration
• Subject refusing to perform prostate biopsy
• Subject who are in a dependency or employment with the sponsor or the investigator Exclusion Criteria Subject Control :
• Subject with histologically confirmed prostate cancer
• Subject with a verified viral infection (HIV or Hepatitis)
• Subject under Finasteride treatment
• Subject with other cancer diagnosed
• Subject unable to sign consent
• Planned longer stay outside the region that prevents compliance with the visit plan
• Subject deprived of liberty, protected adults or vulnerable persons
• Urinary infection ≤ 2 months
• Subject excluding health insurance registration

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Condition: Metastatic Castration-Resistant Prostate Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04077021

Sponsor: Calibr, a division of Scripps Research

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Men ≥ 18 years of age at time of informed consent
• For Part 1 and Part 2: men with metastatic castration resistant prostate cancer (mCRPC) with histologically or cytologically confirmed adenocarcinoma of the prostate as defined by one or more of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
• Patients with treated brain metastasis or LMD are eligible if brain imaging shows no evidence of progression
• Must have prostate-specific antigen (PSA) and/or radiographic progression on AT LEAST One novel androgen receptor (AR)-targeted therapy (abiraterone acetate, enzalutamide).
• Eastern Cooperative Oncology Group performance status of 0-1
• Adequate liver function
• Adequate hematopoietic function
• Testosterone level ≤ 50 ng/mL (or 1.73 nmol/L)
• Patient has a life expectancy of greater than 12 weeks

Exclusion Criteria:

• Patients whose tumors solely exhibit neuroendocrine differentiation or small cell features by histopathology
• Patients with new or progressive brain metastasis or Leptomeningeal Disease (LMD)
• Patients with a history of clinically significant cardiovascular disease such as symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, history of stroke or myocardial infarction within 6 months of enrollment
• Patients with peripheral neuropathy CTCAE Grade >/= 2
• Patients with a known history of hypersensitivity, allergy or intolerance to CCW702 or its excipients
• Patients with untreated or imminent spinal cord compression

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Condition: Biochemically Recurrent Prostate Carcinoma, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IV Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04777071

Sponsor: University of Washington

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Pathologically proven prostate adenocarcinoma
• For the initial staging arm, high risk characteristics, including any of the following:
• Grade group 4-5 and/or
• PSA > 20 ng/mL
• For patients with biochemical recurrence:
• Rising PSA after definitive therapy with prostatectomy or targeted local therapy (including but not limited to external beam radiation therapy, brachytherapy, high-frequency ultrasound, and cryotherapy)
• If post-radical prostatectomy, PSA > 0.2 ng/mL measured > 6 weeks post-operatively and confirmatory persistent PSA greater than 0.2 ng/mL (American Urological Association (AUA) definition for biochemical recurrence
• If post-radiation therapy, PSA that is equal to, or greater than, a 2 mg/mL rise above PSA nadir (American Society of Radiation Oncology (ASTRO) definition for biochemical recurrence)
• For patients undergoing systemic therapy:
• Diagnosis of metastatic castration-resistant prostate cancer
• At least one or more measurable (> 1 cm diameter in short axis) or evaluable lesions by conventional imaging
• Any patient with an equivocal lesion by conventional imaging, regardless of where they are in the course of evaluation or treatment
• No other malignancy within the past 2 years (with the exception of skin basal cell or cutaneous superficial squamous cell carcinoma, superficial bladder cancer, carcinoma in situ in any location, or Rai Stage 0 chronic lymphocytic leukemia, which are allowed)
• Karnofsky performance status (KPS) >= 50, Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) grades 0, 1, or 2
• Ability to understand and willingness to provide informed consent

Exclusion Criteria:

• 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

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Condition: Prostate Cancer, Prostate Disease

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03543189

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male, aged ≥ 18 years
• ECOG Performance Status: 0-1
• Diagnosed with Grade Group 5 prostate cancer (PCa): Gleason grade 9 (4+5 or 5+4) or 10 (5+5) with >30% of cores involved; Any PSA or T-stage
• Pathologically (histologically) proven diagnosis of PCa undergoing their first line of treatment
• Biopsy specimen available
• Patients with oligometastaic disease (defined as ≤3 sites of distant metastatic disease, and/or positive lymph nodes confined to the pelvis) being treated with curative intent are eligible for study participation
• Eligible for definitive RT (HDR + EBRT) + short-term ADT
• Undergoing radiation treatment at Moffitt Cancer Center
• Participants being treated with nivolumab must have normal organ function as defined in protocol.
• Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm turnover) for a total of 31 weeks post-treatment completion; Azoospermic males are exempt from contraceptive requirements; Male participants must be willing to refrain from sperm donation during the entire study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover).

Exclusion Criteria:

• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]) and motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis). Patients with Hashimoto's thyroiditis are eligible to go on study. Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study entry. Corticosteroids with minimal systemic absorption (inhaled or topical steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways)
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or interfere with the interpretation of safety results
• Major surgery or significant traumatic injury that is not recovered at least 14 days before the initiation of prostate radiation therapy
• Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection
• Individuals with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible
• Known medical history of testing positive for human immunodeficiency virus (HIV) or known medical history of acquired immunodeficiency syndrome (AIDS)
• Inadequate hematologic function; hepatic function; pancreatic function
• History of allergy or hypersensitivity to any of the study drugs or study drug components.
• Uncontrolled intercurrent illnesses including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness.
• Social situations that could limit the patient's compliance with study requirements.

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04663997

Sponsor: Canadian Cancer Trials Group

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Histological evidence of prostate cancer with no evidence of small cell component
• Patients must have castration resistance and metastatic disease with evidence of biochemical or imaging progression in the setting of surgical/medical castration
• Progression on treatment with abiraterone and/or enzalutamide, or similar next-generation androgen receptor (AR) targeted therapy
• Evidence of PSMA positive metastatic disease, as assessed on PSMA-PET imaging studies obtained as part of other clinical trial protocols are mandated, provided they are obtained within a timeframe that meets the requirements of this study. The radiopharmaceuticals must be based on a lysine-urea-glutamate backbone, with a 18F or 68Ga radionuclide label.
• Prior orchiectomy, or if on LHRH agonist/antagonist then testosterone < 1.7 nmol/L
• Adequate organ function
• Recover from all previous cancer treatment toxicities to grade ≤ 2 (as per CTCAE v5.0)
• Male subject ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

• Prior treatment with chemotherapy for castration-resistant disease or prior chemotherapy in the castration-sensitive (hormone-sensitive) setting ≤ 1 year prior to enrollment.
• Prior treatment with 177Lu-PSMA (including other radiolabeled therapeutic PSMA-ligands) or radio-immunotherapy. Prior treatment with radium-223 is allowed but requires a minimum of a 6-month interval between the last dose of radium-223 and enrollment.
• Radiotherapy to target lesions (measurable disease) ≤ 12 weeks prior to enrolment.
• Presence of majority (> 50% of extra-osseous lesions) or large (> 5 cm) soft tissue lesions that are negative on PSMA-Ligand PET/CT or PSMA-Ligand PET/MR
• Known parenchymal brain metastases
• Active epidural disease (treated epidural disease is permitted)
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Clinically significant cardiac disease
• Major surgery within 4 weeks of starting study treatment
• Patients with a history of hypersensitivity to the study drug or components
• Patients with a clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or sever psychiatric illness/social situations.

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Condition: Prostatic Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04720157

Sponsor: Novartis Pharmaceuticals

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Participants eligible for inclusion in this study must meet all of the following criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Patients must be adults ≥18 years of age 3. Patients must have an ECOG performance status of 0 to 2 4. Patients must have a life expectancy >9 months as determined by the study investigator 5. Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site) 6. Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader 7. Patients must have at least one documented metastatic bone and/or soft tissue/visceral lesion documented in the following manners within 28 days prior randomization: 1. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans AND/OR 2. Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis AND/OR 3. Visceral metastases of any size or distribution. If a participant has a history of visceral metastases at any time prior to randomization, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes). 8. Patients must have adequate organ function:
• Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL
• Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
• Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation 9. Albumin ≥2.5 g/dL 10. Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial 11. Patients must be: Treatment naïve OR minimally treated with:
• Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of study therapy or after 45 days whatever happens first.
• If received, prior LHRH agonist/antagonist with or without first generation anti-androgen use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.
• Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No CYP17 inhibitor or ARDT exposure for earlier stages of prostate cancer is allowed.

Exclusion Criteria:

• Participants meeting any of the following criteria are not eligible for inclusion in this study. 1. Participants with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy 2. Any prior systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, immunotherapy or biological therapy (including monoclonal antibodies). 3. Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy 4. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed 5. Ongoing participation in any other clinical trial 6. Use of other investigational drugs within 30 days prior to day of randomization 7. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes 8. Transfusion for the sole purpose of making a participant eligible for study inclusion 9. Participants with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with epidural disease, canal disease and prior cord involvement are allowed if those areas have been treated, are stable, and not neurologically impaired. Participants with parenchymal CNS metastasis (or a history of CNS metastasis), that have received prior therapy and are neurologically stable, asymptomatic and not receiving steroids for CNS metastases, are allowed, baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast). 10. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free, treatment free for more than 3 years prior to randomization, or participants with adequately treated non-melanoma skin cancer, superficial bladder cancer are eligible. 11. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance). 12. Active clinically significant cardiac disease defined as any of the following:
• NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
• History of familial long QT syndrome or known family history of Torsades de Pointes
• Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature 13. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study 14. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression 15. Any condition that precludes raised arms position 16. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed. 17. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF

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