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Monthly Update Report for Trials Started in May 2026


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1: Summary data from new trials identified for Prostate Cancer.


Overview

Number of Trials: 14

These 14 trials focus on prostate cancer across various stages and treatment settings. Most trials target metastatic castration-resistant prostate cancer (mCRPC) with novel therapies including PARP inhibitors, androgen receptor pathway inhibitors (ARPIs), T-cell engagers, CAR-T therapies, and radiopharmaceuticals. Several trials explore focal radiation therapy, active surveillance strategies, and quality-of-life interventions. Genomic and biomarker-driven patient selection is prominent, particularly PSMA-positive disease and homologous recombination repair (HRR) mutations. Trials also investigate neoadjuvant and adjuvant immunotherapy, wearable technology for symptom monitoring, and testosterone replacement safety in low-risk disease.

Common Criteria Across Trials

Common Inclusion

  • Histologically confirmed adenocarcinoma of the prostate
  • Age ≥18 years
  • ECOG performance status 0-2
  • Adequate organ and marrow function (ANC ≥1500, platelets ≥100,000, hemoglobin ≥8-9 g/dL)
  • Castrate testosterone level <50 ng/dL (for advanced disease trials)
  • Metastatic disease documented by imaging (CT, MRI, bone scan, or PSMA PET)
  • Progressive disease (PSA or radiographic)
  • Prior treatment with androgen receptor pathway inhibitors (ARPIs)
  • Willing to provide informed consent and comply with study requirements

Common Exclusion

  • Small cell or neuroendocrine differentiation (except specific trials)
  • Active brain metastases or spinal cord compression unless stable and asymptomatic
  • Prior malignancy within 3 years (with exceptions)
  • Active autoimmune disease requiring systemic therapy
  • Uncontrolled infection or febrile illness
  • Grade >2 treatment-related toxicities from prior therapy
  • Seizure history or conditions predisposing to seizures
  • Uncontrolled cardiac disease or recent myocardial infarction
  • Concurrent use of prohibited medications (CYP inhibitors/inducers, P-gp inhibitors)
  • Known hypersensitivity to study agents

Outcomes Summary

Primary Outcomes

Secondary Outcomes


2: Extracted Trials with New Information


Trials with Special Criteria

Genomic / Biomarker Trials

Unique or Unusual Criteria

Trials with Emerging Treatments


3: Individual Trial Overviews


NCT06844383

A Randomized Open-label Phase 2 Study of TALazoparib With or Without ENzaluTamide in Patients With Metastatic Castration-Resistant Prostate Cancer and HRR Mutations After Progression on Abiraterone Acetate Genomic-based

Organization/Sponsor: Prostate Cancer Clinical Trials Consortium


Example patient: A 67-year-old man with metastatic castration-resistant prostate cancer harboring a BRCA2 mutation, ECOG status 1, testosterone <50 ng/dL on continuous ADT, who progressed on abiraterone acetate with rising PSA and new bone metastases, with no prior PARP inhibitor or platinum chemotherapy exposure.

Phase 2

Interventions

  • Drug: Talazoparib
    Summary: Talazoparib is a PARP inhibitor that blocks DNA repair mechanisms, causing cancer cell death in HRR gene-mutated metastatic castration-resistant prostate cancer. FDA approved for use in combination with enzalutamide. Source: Web Search Summary.
  • Drug: Talazoparib with enzalutamide
    Summary: Combination regimen where enzalutamide inhibits androgen receptor signaling critical for prostate cancer growth, while talazoparib blocks DNA repair. Enzalutamide induces CYP450 enzymes affecting drug metabolism. Sources: FDA label, NCI Thesaurus.

Key Inclusion

  • Metastatic castration-resistant prostate cancer with HRR mutation (BRCA1, BRCA2, ATM, CDK12, CHEK2, PALB2, MLH1, NBN, ATR, FANCA, MRE11A, RAD51C)
  • Prior abiraterone acetate with prednisone for mHSPC or locally advanced disease with progression
  • Progressive disease with PSA progression, soft tissue progression, bone progression, or new PSMA PET lesions
  • Testosterone levels <50 ng/dL with surgical or medical castration
  • ECOG performance status ≤1
  • Age ≥18 years
  • Adequate organ function including ANC ≥1500/µl, hemoglobin ≥9g/dl, platelets ≥100,000/µl
  • Willing to remain on treatment despite PSA progression unless clinically deteriorating

Key Exclusion

  • Prior PARP inhibitor treatment
  • Prior platinum-based chemotherapy for prostate cancer
  • Prior ARPI other than abiraterone acetate with prednisone for ≥12 weeks in mCRPC setting
  • History of seizure or conditions predisposing to seizure
  • Current use of strong CYP2C8 inhibitors/inducers, strong CYP3A4 inducers, or potent P-gp inhibitors
  • Untreated brain metastases or spinal cord compression
  • Active malignancy or diagnosis of another malignancy within 3 years requiring active treatment
  • Grade >2 treatment-related toxicity from prior therapy except alopecia or peripheral neuropathy

NCT07529717

Phase I/II Dose Escalation & Dose Optimization Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD8359, a CD8-guided T Cell-engaging Antibody That Targets STEAP2, in Adult Participants With Prostate Cancer

Organization/Sponsor: AstraZeneca


Example patient: A 68-year-old man with metastatic castration-resistant prostate adenocarcinoma, testosterone 25 ng/dL, PSA 15 ng/mL, disease progression on enzalutamide and docetaxel, adequate organ function, no cardiac arrhythmias or autoimmune disorders.

Phase 1, Phase 2

Interventions

  • Biological: AZD8359
    Summary: AZD8359 is a CD8-biased T cell engager targeting STEAP2 in prostate cancer, designed to enhance therapeutic efficacy by redirecting T cells to tumor cells. It is being evaluated for safety, tolerability, and effectiveness in metastatic prostate cancer (Source: Web Search).

Key Inclusion

  • Histologically confirmed adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer
  • Surgically or medically castrated with serum testosterone ≤50 ng/dL
  • PSA value at screening ≥1 ng/mL
  • Evidence of disease progression within 6 months prior to screening
  • Part A: At least 2 prior systemic therapies including one androgen receptor pathway inhibitor and one taxane regimen
  • Part B: Received androgen receptor pathway inhibitor for metastatic hormone sensitive or castration resistant prostate cancer
  • Adequate organ function
  • Body weight ≥35 kg

Key Exclusion

  • Clinically relevant cardiac abnormalities such as QT prolongation or uncontrolled cardiac arrhythmias
  • Prior treatment-related adverse events not resolved to Grade ≤2
  • History of Grade ≥3 cytokine release syndrome
  • History of Grade ≥2 immune effector cell-associated neurotoxicity syndrome with prior therapy
  • Active or prior documented autoimmune or inflammatory disorders within the past 3 years
  • Prior exposure to any STEAP2 targeted agents or T cell engagers for prostate cancer
  • Part B Module 1 and 2: Prior taxane treatment for metastatic castration resistant prostate cancer

NCT07518888

Exercise-induced Steroid Changes in Active Surveillance for Prostate Cancer

Organization/Sponsor: University of Miami


Example patient: A 62-year-old English-speaking male with localized prostate cancer on active surveillance, physically active with no cardiovascular disease or mobility limitations, not on steroid-affecting medications.

Phase N/A

Interventions

  • Behavioral: High-Intensity Interval Training (HIIT) Exercise
    Summary: A cardiovascular exercise alternating short periods of intense anaerobic exercise with less intense recovery periods, used to study steroid metabolism changes in prostate cancer patients (NCI Thesaurus).

Key Inclusion

  • Males 18 to 80 years old
  • Diagnosis of localized prostate cancer
  • Currently under active surveillance
  • Ability to perform moderate-to-high intensity physical activity
  • Able to independently perform activities of daily living without mobility limitations
  • Ability to read, write, speak, and understand English

Key Exclusion

  • Currently receiving treatment for prostate cancer
  • Diagnosis of metastatic prostate cancer
  • Medical conditions contraindicating exercise
  • Uncontrolled cardiovascular or circulatory diseases, hypertension, and diabetes
  • Ongoing use of medications affecting steroid metabolism

NCT07568756

Utilization of Flotufolastat 18F PET for Post-Focal Therapy Prostate Cancer Evaluation Genomic-based

Organization/Sponsor: University of California, Irvine


Example patient: A 62-year-old man with newly diagnosed low-risk prostate adenocarcinoma confined to one prostatic lobe, PSA of 6.5, genomic classifier showing low-risk disease, scheduled for focal HIFU therapy with multiparametric MRI and fusion biopsy.

Phase N/A

Interventions

  • Drug: Flotufolastat F18 PET
    Summary: POSLUMA is a fluorine-18 labeled radiohybrid PSMA ligand for PET imaging that targets and binds to PSMA-expressing prostate cancer cells, enabling visualization of metastatic or recurrent disease. PSMA is overexpressed on prostate tumor cells. Sources: FDA label, NCI Thesaurus.

Key Inclusion

  • Age 18 years or greater
  • Prostate adenocarcinoma
  • Planned focal therapy (cryotherapy, HIFU, or NanoKnife)
  • Multiparametric-MRI imaging planned
  • Planned pre- and post-treatment MRI-fusion biopsy

Key Exclusion

  • Prior treatment for prostate malignancy (radiation, focal therapy, or systemic therapy)
  • Genomic classifiers signifying intermediate or high-risk disease
  • PSA >10
  • High-risk prostate cancer diagnosed by biopsy
  • Bilateral prostatic lobe disease

NCT07468903

Phase II Trial of Focal Radiation Therapy in Patients With Prostate Cancer

Organization/Sponsor: Jonsson Comprehensive Cancer Center


Example patient: A 58-year-old man with newly diagnosed Gleason 6 prostate adenocarcinoma confirmed by systematic biopsy, mpMRI-identified focal lesion comprising 25% of prostate volume, ECOG status 0, and negative PSMA PET scan for metastases.

Phase II

Interventions

  • Procedure: Questionnaire Administration
    Summary: Patient self-reported outcome tool measuring quality of life and treatment effects, assessing psychological and physical impacts with no direct biological mechanism (NCI Thesaurus, Web Search).
  • Diagnostic Test: PSMA PET Scan
    Summary: Imaging technique using 68Ga-PSMA-11 to target prostate-specific membrane antigen on cancer cells, improving detection of recurrence and staging in advanced prostate cancer (NCI Thesaurus, Web Search).
  • Diagnostic Test: Multiparametric Magnetic Resonance Imaging
    Summary: Diagnostic tool combining T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging to detect and stage prostate cancer, guiding biopsies and treatment planning (Web Search).
  • Radiation: High-Dose Rate Brachytherapy
    Summary: Internal radiation therapy delivering high doses directly to prostate cancer using temporary radioactive sources, minimizing damage to surrounding tissues, often combined with external beam radiotherapy (Web Search).
  • Procedure: Biospecimen Collection
    Summary: Gathering tissue and fluid samples for testing and research to analyze genetic and molecular features, aiding in understanding cancer mechanisms and developing targeted therapies (NCI Thesaurus, Web Search).
  • Procedure: Biopsy Procedure
    Summary: Removal of tissue specimens for microscopic examination to establish diagnosis, determining cancer type and guiding treatment decisions (NCI Thesaurus, Web Search).

Key Inclusion

  • Histologically confirmed prostate adenocarcinoma within 90 days via systematic biopsy
  • Multiparametric MRI confirmed lesion(s)
  • No distant or locally advanced disease on staging exams
  • ECOG/Zubrod performance status 0/1
  • Age ≥ 40

Key Exclusion

  • Radiographic nodal or distant metastatic disease
  • Lesion(s) comprising > 40% of total prostate volume
  • Prior radiotherapy to the pelvis
  • Gleason score > 6 disease outside intended target region(s)

NCT07296887

Implement and Evaluate the CARE Tool in a Randomized Trial

Organization/Sponsor: Washington University School of Medicine


Example patient: A 62-year-old English-speaking man diagnosed with primary prostate cancer 8 months ago, currently receiving treatment at Siteman Cancer Center, with full cognitive capacity to provide informed consent.

Phase N/A

Interventions

  • Behavioral: CARE Tool Training
    Summary: Training intervention to enhance care strategies and patient support coordination for cancer patients, improving outcomes through structured care delivery (Summary of Web Search).
  • Behavioral: CARE Tool
    Summary: Web-based tool providing information on cancer care costs, health insurance, and financial resources to improve patient decision-making and reduce anxiety (Summary of Web Search).
  • Behavioral: Financial education information
    Summary: Educational intervention providing financial information to reduce barriers and improve understanding of cancer treatment costs and screening adherence (Summary of Web Search, NCI Thesaurus).

Key Inclusion

  • Age 18 and over
  • Primary or recurrent diagnosis of gynecologic, prostate, lung, or colorectal cancer in the last 12 months
  • Receiving cancer treatment from Siteman Cancer Center, Delbert Day Cancer Institute at Phelps Health, or Alton Memorial Hospital
  • Self-reported ability to read and speak English

Key Exclusion

  • Under the age of 18
  • Not diagnosed with gynecologic, prostate, lung, or colorectal cancer within the previous 12 months from recruitment
  • Not receiving care at Siteman Cancer Center, Delbert Day Cancer Institute at Phelps Health, or Alton Memorial Hospital
  • Cannot give consent due to cognitive or emotional barriers

NCT07570979

An Open-label, Multi-center, First in Human Phase I Global Dose Escalation and Expansion Study of INR731 Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer

Organization/Sponsor: Novartis


Example patient: A 68-year-old man with metastatic castration-resistant prostate adenocarcinoma, ECOG PS 1, castrate testosterone level of 35 ng/dL on ongoing GnRH agonist therapy, with bone and lymph node metastases on recent CT scan, previously treated with docetaxel and abiraterone with disease progression.

Phase I

Interventions

  • Drug: INR731
    Summary: INR731 is a novel investigational drug targeting androgen receptor pathways for castration-resistant prostate cancer, currently under evaluation for safety and efficacy (Summary of Web Search).
  • Drug: Abiraterone
    Summary: Abiraterone acetate is a CYP17 inhibitor that blocks androgen synthesis by inhibiting 17α-hydroxylase/C17,20-lyase, used with prednisone for metastatic CRPC and high-risk CSPC (FDA label).
  • Drug: Enzalutamide
    Summary: Enzalutamide is an androgen receptor inhibitor that blocks AR signaling and induces CYP450 enzymes, indicated for castration-resistant and castration-sensitive prostate cancer (FDA label).
  • Therapy: Androgen deprivation therapy (ADT)
    Summary: ADT reduces serum androgen levels through surgical or medical means to slow prostate cancer growth, requiring monitoring for side effects (NCI Thesaurus, Web Search).

Key Inclusion

  • Histological/cytological confirmation of adenocarcinoma of the prostate
  • At least 1 metastatic lesion on CT, MRI, or bone scan within 28 days prior to C1D1
  • Castrate level of testosterone (<50 ng/dL or <1.7 nmol/L)
  • ECOG Performance Status ≤2
  • mCRPC patients progressed on or not candidates for other standard of care
  • Combination expansion patients must be 1L mCRPC with no prior mCRPC treatment
  • Ongoing ADT via orchiectomy and/or GnRH analog or inhibitor allowed
  • Prior taxane, PARP inhibitor, and lutetium Lu 177 vipivotide tetraxetan allowed

Key Exclusion

  • Age < 18 years old
  • Non-adenocarcinoma histology of the prostate
  • Biochemical recurrence only without metastatic disease on imaging
  • Previously treated with a cereblon-based degrader
  • HIV+ or immune compromised patients
  • Use of agents known to prolong QT interval unless permanently discontinued
  • Treatment with investigational agent within 7 days or 5 half-lives of C1D1

NCT07027124

Neoadjuvant ADT and Darolutamide With Pembrolizumab, Followed by Adjuvant Pembrolizumab in NCCN High-risk and Molecularly Stratified Prostate Cancer Patients Genomic-based

Organization/Sponsor: Icahn School of Medicine at Mount Sinai


Example patient: A 62-year-old male with newly diagnosed Gleason 4+3 prostate adenocarcinoma, Decipher score 0.60 with Luminal B subtype, no metastases, ECOG performance status 0, and adequate organ function.

Phase N/A

Interventions

  • Drug: Lupron
    Summary: Lupron is a GnRH agonist that suppresses pituitary production of testosterone by binding GnRH receptors, leading to castration-level testosterone in males for prostate cancer treatment (FDA label, NCI Thesaurus).
  • Drug: Pembrolizumab
    Summary: Pembrolizumab is a humanized monoclonal antibody that blocks PD-1 receptor on T cells, preventing ligand binding and enhancing immune-mediated tumor destruction in various cancers (FDA label, NCI Thesaurus).
  • Drug: Darolutamide
    Summary: Darolutamide is an androgen receptor inhibitor that blocks androgen-induced receptor activation, preventing nuclear translocation and transcription of genes regulating prostate cancer cell proliferation (FDA label, NCI Thesaurus).

Key Inclusion

  • Male age ≥18 years with histopathologically confirmed prostate adenocarcinoma
  • Unfavorable intermediate and high-risk localized or locally advanced prostate cancer with Gleason score ≥7 (4+3)
  • Decipher Genomic Classifier >0.45 and/or Luminal B subtype
  • Absence of distant metastasis or non-regional nodal involvement
  • Performance status 0-1 by ECOG criteria
  • Adequate organ and marrow function including ANC ≥1,500/mcL, platelets ≥100,000/mcL, hemoglobin ≥9 g/dL
  • Adequate hepatic function with total bilirubin ≤1.5 mg/dL, AST/ALT ≤2.5x ULN
  • Creatinine clearance ≥30 mL/min

Key Exclusion

  • Metastatic disease or Gleason score ≤7 (3+4)
  • Biopsy Decipher score ≤0.45
  • Prior hormonal therapy, radiation therapy, or chemotherapy for prostate cancer (with specified exceptions)
  • Active cardiac disease within 6 months including myocardial infarction or congestive heart failure
  • Prior treatment with androgen receptor inhibitors or checkpoint inhibitors
  • Active infection requiring systemic therapy within 7 days
  • Chronic systemic steroid therapy exceeding 10 mg daily prednisone equivalent
  • Active autoimmune disease requiring systemic therapy in past 2 years

NCT07635238

Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions - A Randomized Trial (DESTINATION 2)

Organization/Sponsor: Memorial Sloan Kettering Cancer Center


Example patient: A 65-year-old man with newly diagnosed Grade Group 2 prostate adenocarcinoma, clinical stage T2a, PSA 12 ng/mL, PIRADS 4 lesion measuring 1.8cm on MRI, prostate volume 75mL, IPSS score 10, no prior prostate treatments, and no metastatic disease.

Phase N/A

Interventions

  • Radiation: MR-guided Stereotactic Body Radiation Therapy
    Summary: Stereotactic body radiation therapy using MR imaging to define and localize the treatment area, delivered in extreme hypofractionation (2 fractions) for prostate cancer (NCI Thesaurus).

Key Inclusion

  • Pathologically confirmed prostate adenocarcinoma
  • Grade Group 1, 2, or 3
  • PSA less than 20 ng/mL prior to ADT if used
  • Clinical stage TX, T1, or T2; up to radiological T3a on MRI
  • MRI-visible tumor with PIRADS v2 scores 3, 4, or 5
  • Tumor nodule less than 2.5cm in maximal dimension
  • Prostate volume less than or equal to 90mL
  • No evidence of nodal or distant metastatic disease

Key Exclusion

  • History of previous prostate radiation, surgery including TURP, or local treatments
  • High grade disease (GG3) occult to MRI-defined lesion
  • Contraindications to MRI (pacemaker, metal implant, claustrophobia)
  • IPSS Score greater than 19
  • Severe GU symptoms precluding extreme hypofractionation
  • Comorbidities predisposing to significant toxicity (e.g. inflammatory bowel disease)
  • Active infection requiring parenteral antibiotics
  • Patients needing greater than 6 months of ADT

NCT07535541

A Feasibility Study of Biometric Measurements Via Wearable Smart Watch Technology for Evaluation of Vasomotor Symptoms in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer (BioWEAR)

Organization/Sponsor: University of Virginia


Example patient: A 65-year-old male with metastatic prostate cancer on ADT for 3 months with castrate testosterone of 20 ng/dL, experiencing daily hot flashes since starting treatment, ECOG 1, owns an iPhone 12, and has stable PSA.

Phase N/A

Interventions

  • Device: VMS logging
    Summary: VMS logging via Embrace Plus smartwatch monitors physiological data including real-time health metrics to evaluate vasomotor symptoms in patients on androgen deprivation therapy. Source: Summary of Web Search.

Key Inclusion

  • Male aged ≥18 years
  • Diagnosis of prostate cancer
  • Receiving active ADT with castrate testosterone <50 ng/dL
  • VMS occurring minimum once daily after ADT initiation
  • ADT expected to continue minimum 4 weeks
  • Own Bluetooth 5 compatible smartphone
  • ECOG performance status 0, 1, or 2
  • Ability to read, speak, and understand English

Key Exclusion

  • Wrist circumference <95 mm or >222 mm
  • Allergic to silicone
  • VMS present prior to ADT initiation
  • Active febrile illness (temperature >38°C)
  • Inability to press smartwatch button
  • Receiving experimental prostate cancer therapy
  • Evidence of prostate cancer progression per PCWG3 criteria

NCT07488923

A Phase 1 First-In-Human Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of ML261, an Autologous Anti-DLL3 CAR + CARD11-PIK3R3 Fusion T Cell Therapy, in Participants With Relapsed/Refractory Small Cell Lung Cancer or Select Neuroendocrine Carcinomas Genomic-based

Organization/Sponsor: Moonlight Bio, Inc


Example patient: A 62-year-old man with metastatic relapsed small cell lung cancer with DLL3 expression on biopsy, ECOG PS 1, who progressed after platinum-based chemotherapy and has no brain metastases or active infections.

Phase 1

Interventions

  • Biological: ML261
    Summary: ML261 is an autologous CAR T cell therapy targeting DLL3 with CARD11-PIK3R3 fusion for enhanced T cell function. It genetically modifies patient T cells to recognize and attack DLL3-expressing cancer cells in relapsed/refractory small cell lung cancer and neuroendocrine carcinomas. Source: Web Search Summary.

Key Inclusion

  • ≥18 years of age
  • At least one prior line of systemic standard of care anti-cancer therapy
  • Documented radiological disease progression/relapse with measurable disease per RECIST v1.1
  • Histologically/cytologically confirmed R/R SCLC, GEP-NEC, high-grade NEPC, or epNEC with DLL3 expression
  • Small cell/neuroendocrine tumor cell percentage >50% (>20% for high-grade NEPC)
  • ECOG Performance Score 0 or 1
  • Life expectancy ≥12 weeks
  • Adequate hematologic and end-organ function

Key Exclusion

  • Prior DLL3-targeted CAR T or genetically engineered adoptive T cell therapy
  • Prior allogeneic organ or bone marrow transplant
  • Major surgery within 4 weeks or anticipated during study
  • Active brain metastases requiring steroids within 2 weeks
  • Active systemic autoimmune disease requiring immunosuppressive agents
  • Active infection requiring systemic therapy within 14 days of leukapheresis
  • Myocardial infarction within 6 months or NYHA Class III-IV heart failure
  • Interstitial lung disease or active pneumonitis requiring treatment

NCT07611110

A Phase III, Multicentre, Randomised Controlled Study to Evaluate the Efficacy and Safety of AZD2265 (FPI-2265) ²²⁵Ac-PSMA-I&T Compared With Standard of Care in Patients With PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)

Organization/Sponsor: AstraZeneca


Example patient: A 68-year-old man with metastatic castration-resistant prostate adenocarcinoma, ECOG 1, castrate testosterone on ADT, positive PSMA PET scan, previously treated with 4 cycles of lutetium-177-PSMA, docetaxel chemotherapy, and enzalutamide, now with progressive disease and bone metastases.

Phase III

Interventions

  • Drug: Radium-223
    Summary: Alpha particle-emitting radiotherapeutic agent that targets bone tissue and accumulates in osteoblastic lesions, forming complexes with hydroxyapatite and causing DNA double-strand breaks in bone metastases; indicated for castration-resistant prostate cancer with symptomatic bone metastases without visceral disease (FDA label, NCI Thesaurus).
  • Drug: Rezvilutamide
    Summary: Orally bioavailable androgen receptor antagonist that competitively binds to AR, prevents androgen-induced receptor activation, and inhibits transcription of AR-responsive genes regulating prostate cancer cell proliferation (NCI Thesaurus).
  • Drug: Darolutamide
    Summary: Androgen receptor inhibitor that blocks androgen-induced receptor activation and prevents transcription of AR-responsive genes; indicated for non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer, including combination with docetaxel (FDA label, NCI Thesaurus).
  • Drug: Apalutamide
    Summary: Androgen receptor antagonist that prevents androgen-induced receptor activation and inhibits transcription of AR-responsive genes; indicated for metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer (FDA label, NCI Thesaurus).
  • Drug: Enzalutamide
    Summary: Androgen receptor inhibitor that blocks AR signaling and induces cytochrome P450 enzymes; indicated for castration-resistant, metastatic castration-sensitive, and non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence; FDA approved 2012 (FDA label, NCI Thesaurus).
  • Drug: Abiraterone
    Summary: CYP17 inhibitor that blocks 17α-hydroxylase/C17,20-lyase enzyme to reduce testosterone production in testes and adrenals; indicated with prednisone for metastatic castration-resistant and metastatic high-risk castration-sensitive prostate cancer (FDA label, NCI Thesaurus).
  • Drug: Cabazitaxel
    Summary: Semi-synthetic taxane that binds and stabilizes tubulin, inhibiting microtubule depolymerization and causing G2/M cell cycle arrest; indicated with prednisone for metastatic castration-resistant prostate cancer after docetaxel; penetrates blood-brain barrier and resists P-glycoprotein efflux (FDA label, NCI Thesaurus).
  • Drug: AZD2265
    Summary: Radiopharmaceutical targeting PSMA that delivers alpha particle radiation directly to prostate cancer cells; under investigation for metastatic castration-resistant prostate cancer (Summary of Web Search).

Key Inclusion

  • Age ≥18 years with adenocarcinoma of prostate
  • Progressive mCRPC with castrate testosterone levels on ADT or post-orchiectomy
  • At least one metastatic lesion suitable for repeated imaging assessment
  • Previously treated with at least 2 cycles of PSMA-directed β-emitting radioconjugate
  • Previously treated with at least 1 taxane-based chemotherapy regimen
  • Previously treated with at least 1 ARPI (enzalutamide, abiraterone, etc.)
  • Positive PSMA PET/CT scans with ⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL
  • ECOG performance status 0 to 2 with adequate organ and bone marrow function

Key Exclusion

  • Prior treatment with α-emitting molecular targeted therapeutic radioconjugate (radium-223 permitted)
  • Progression on PSMA-directed β-emitting radioconjugate before Cycle 3
  • Receipt of >6 cycles of PSMA-directed β-emitting therapeutic radioconjugate
  • History of another primary malignancy with exceptions
  • Persistent toxicities CTCAE Grade ≥2 from previous anticancer therapy with exceptions
  • Spinal cord compression or brain metastases unless asymptomatic, stable, and steroid-free for ≥4 weeks
  • Clinically significant ECG abnormalities with exceptions

NCT07590934

A Phase Ib/II, Open-label, Multi-centre, Platform Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Multiple Anti-Cancer Agents in Metastatic Prostate Cancer

Organization/Sponsor: AstraZeneca


Example patient: A 68-year-old man with metastatic castration-resistant prostate adenocarcinoma, ECOG 1, testosterone <50ng/dL on ADT, with PSMA-positive bone and lymph node metastases progressing after one line of abiraterone, no CNS involvement or prior seizures.

Phase Ib, Phase II

Interventions

  • Imaging agent: AZD2287
    Summary: A compound that enables or improves visualization of body structures or functions for medical imaging (NCI Thesaurus).
  • Chemotherapy: Docetaxel
    Summary: A microtubule inhibitor that binds and stabilizes tubulin, inhibiting microtubule disassembly, causing cell-cycle arrest at G2/M phase and cell death; indicated for castration-resistant prostate cancer and other solid tumors (FDA label, NCI Thesaurus).
  • PARP inhibitor: AZD9574
    Summary: An investigational PARP inhibitor targeting DNA repair pathways to inhibit cancer growth in advanced solid tumors including prostate cancer (Summary of Web Search).
  • Radiopharmaceutical: AZD2265 (FPI-2265)
    Summary: A radiopharmaceutical agent targeting prostate-specific membrane antigen (PSMA) labeled with alpha-emitting radioisotope actinium Ac 225 (NCI Thesaurus).

Key Inclusion

  • Histologically confirmed adenocarcinoma of the prostate
  • ECOG performance status 0 or 1
  • Received at least one novel androgen receptor pathway inhibitor (ARPI)
  • One or more unresectable metastatic lesions
  • Castrate level of serum testosterone (<50ng/dL or <1.7nmol/L)
  • Progressive metastatic castration-resistant prostate cancer (mCRPC)
  • Sub study 1: Single line of ARPI only
  • Sub study 1: PSMA positive mCRPC with tracer uptake greater than liver

Key Exclusion

  • Non adenocarcinomatous forms of prostate cancer (small cell, neuroendocrine, sarcomatoid)
  • Central nervous system metastases
  • Symptomatic malignant spinal cord compression
  • Leptomeningeal carcinomatosis
  • Previous or concurrent cancer distinct from prostate cancer
  • History of interstitial lung disease or non-infectious pneumonitis
  • Sub study 1: History of uncontrolled seizures or requirement for >2 antiepileptic drugs
  • Sub study 1: Received prior AZD9574 or >1 prior line of PARP inhibitor-based regimen

NCT07278362

Safety of Intramuscular Testosterone Replacement Therapy in Hypogonadal Patients With Prostate Cancer Under Active Surveillance

Organization/Sponsor: University of Miami


Example patient: A 62-year-old male with newly diagnosed low-risk prostate cancer on active surveillance, confirmed by two biopsies, with testosterone level of 250 ng/dL, Aging Male's Symptoms Score of 30, PSA of 6 ng/mL, hematocrit of 45%, and no history of testosterone therapy or cardiovascular disease.

Phase N/A

Interventions

  • Drug: Testosterone cypionate
    Summary: Testosterone cypionate is an androgen receptor agonist that provides exogenous testosterone replacement in hypogonadal males by supplementing deficient testosterone levels. It inhibits gonadotropin secretion and is administered intramuscularly. This trial assesses its safety in low-risk prostate cancer patients under active surveillance. Sources: FDA label, NCI Thesaurus, Web Search.

Key Inclusion

  • Males aged ≥18 years old
  • Newly diagnosed low-risk prostate cancer confirmed by fusion guided biopsy
  • Second confirmatory biopsy within last 12 months
  • Undergoing active surveillance
  • Two testosterone levels <300 ng/dL taken before 10am
  • Symptoms of low testosterone (Aging Male's Symptoms Score >27)
  • Willing to obtain testosterone medication

Key Exclusion

  • History of TRT within past year or current TRT use
  • Gleason score 7 (Grade Group 2) or higher prostate cancer
  • PSA >10 ng/mL at baseline
  • Hematocrit >51% at baseline
  • T3 or T4 disease
  • Uncontrolled cardiovascular disease or sleep apnea
  • History of breast cancer