Neoplasms

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Carcinoma

Prostatic Neoplasms

Recurrence

Urogenital Neoplasms

Genital Neoplasms, Male

Disease Attributes

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Hormones

Radiopharmaceuticals

Patients with BCR prostate cancer, after definitive surgery or radiation therapy, who have PSMA-positive disease and have not yet initiated lifelong hormone therapy.

Patients with PSMA-positive mCRPC who have exhausted all satisfactory or available approved treatment options.

Administered intravenously per dose escalation scheme. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 6-week cycle for up to 4 cycles.

[Ac-225]-PSMA-62 (mCRPC)

Administered intravenously per dose escalation scheme. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 8-week cycle for up to 2 cycles.

[Ac-225]-PSMA-62 (BCR)

Richard Cioci

ACCEL is a multicenter, open label phase I/II study of \[Ac-225\]-PSMA-62 in participants with prostate-specific membrane antigen (PSMA)-positive prostate cancer.

The primary aim of the phase I study is to evaluate the safety and tolerability of \[Ac-225\]-PSMA-62 to determine recommended phase II doses for patients with mCRPC and BCR prostate cancer. The aim of the phase II study for patients with mCRPC is to evaluate the efficacy of \[Ac-225\]-PSMA-62.

[Ac-225]-PSMA-62 Trial in Biochemically Recurrent and Metastatic Castration Resistant Prostate Cancer

[Ac-225]-PSMA-62 Phase I/II Clinical Trial to Characterize Efficacy, Safety, Tolerability, and Dosimetry in Biochemically Recurrent and Metastatic Castration Resistant Prostate Cancer (ACCEL)

Treatment emergent adverse events (TEAEs) and dose limiting toxicities (DLTs) for \[Ac-225\]-PSMA-62

To assess safety and tolerability of \[Ac-225\]-PSMA-62

BCR only: Preliminary efficacy assessment

mCRPC only: Preliminary efficacy assessment based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (soft tissue) and the Prostate Cancer Working Group 3 (PCWG3) criteria (bone) per investigator review

Evaluation of the biodistribution and radiation dosimetry of \[Ac-225\]-PSMA-62 to normal organs

To determine the effect of \[Ac-225\]-PSMA-62 on prostate-specific antigen (PSA) kinetics

To determine the effect of \[Ac-225\]-PSMA-62 on patient reported outcomes (PROs) responses scored from 0 ("never", "none", "not at all") to 5 ("almost constantly", "very severe", "very much") on the frequency, severity and/or interference of symptoms related to adverse events

Eli Lilly and Company

POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Immune System Diseases

Hypersensitivity

Androgens

Prolactin Release-Inhibiting Factors

Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months.

Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months.

Darolutamide (BAY1841788, Nubeqa)

Placebo matching darolutamide

Luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonists

Bayer Clinical Trials Contact

Researchers are looking for a better way to treat men at high-risk of biochemical recurrence (BCR) of prostate cancer.

BCR means that in men who had prostate cancer and were treated by either surgery and/ or radiation therapy, the blood level of a specific protein called PSA rises. PSA is a marker of prostate cancer cells activity. The PSA increase means that the cancer has come back even though conventional imaging such as computed tomography (CT) scans, magnetic resonance imaging (MRI) and bone scans does not show any lesion of prostate cancer. Recently a more sensitive imaging method called prostate-specific membrane antigen \[PSMA\] positron emission tomography \[PET\]) /computed tomography \[CT\]) scan may identify prostate cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of their cancer spreading to other parts of the body, particularly when PSA levels raised to a certain limit within a short period of time after local therapies. Once the cancer spreads to other parts of the body, it can become even harder to treat.

In men with prostate cancer, male sex hormones (also called androgens) like testosterone can help the cancer grow and spread. To reduce androgens levels in these patients, there are treatments that block androgens production in the body called androgen deprivation therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate cancer growth and spread is to block the action of androgen receptors on prostate cancer cells called androgen receptor inhibitors (ARIs). The new generation ARIs including darolutamide can block the action of androgens receptors and are available for the treatment of prostate cancer in addition to ADT. It is already known that men with prostate cancer benefit from these treatments.

The main objective of this study is to learn if the combination of darolutamide and ADT prolongs the time that the participants live without their cancer getting worse, or to death due to any cause, compared to placebo (which is a treatment that looks like a medicine but does not have any medicine in it) and ADT given for a pre-specified duration of 24 months.

To do this, the study team will measure the time from the date of treatment allocation to the finding of new cancer spread in the participants by using PSMA PET/CT, or death due to any cause. The PSMA PET/CT scans is performed using a radioactive substance called a "tracer" that specifically binds to the prostate-specific membrane antigen (PSMA) which is a protein often found in large amounts on prostate cancer cells.

To avoid bias in treatment, the study participants will be randomly (by chance) allocated to one of two treatment groups. Based on the allocated treatment group, the participants will either take darolutamide plus ADT or placebo plus ADT twice daily as tablets by mouth. The study will consist of a test (screening) phase, a treatment phase and a follow-up phase. The treatment duration is pre-specified to be 24 months unless the cancer gets worse, the participants have medical problems, or they leave the study for any reason. In addition, image guided radiotherapy (IGRT) or surgery is allowed and your doctor will explain the benefits and risks of this type of therapy.

During the study, the study team will:

* take blood and urine samples.
* measure PSA and testosterone levels in the blood samples
* do physical examinations
* check the participants' overall health
* examine heart health using electrocardiogram (ECG)
* check vital signs
* check cancer status using PSMA PET/CT scans, CT, MRI and bone scans
* take tumor samples (if required)
* ask the participants if they have medical problems

About 30 days after the participants have taken their last treatment, the study doctors and their team will check the participants' health and if their cancer worsened. The study team will continue to check this and regularly ask the participants questions about medical problems and subsequent therapies until they leave the study for any reason or until they leave the study for any reason or until the end of the study, whatever comes first.

A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies

A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide Plus Androgen Deprivation Therapy (ADT) Compared With Placebo Plus ADT in Patients With High-risk Biochemical Recurrence (BCR) of Prostate Cancer

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

FACT-P is a multidimension, selfreport QoL instrument specifically designed for patients with prostate cancer. It consists of 39 questions items, made up by 2 parts: the 27 questions for functional assessment of cancer therapy general (FACT-G) and 12 prostate cancer subscale questions. It assesses 4 main domains which are: physical (n=7), social/family (n=7), emotional (n=6) and functional wellbeing (n=7).

Bayer

Adenocarcinoma

Gallium 68 PSMA-11

Administration of Ga-68-PSMA-11 and acquisition of PET/CT

Ga-68-PSMA-11 is produced via a lyophilized Sterile Cold kit. Ga-68 is eluted from a Ge-68/Ga-68 generator into a vial containing the premixed peptide and buffer. PSMA-11 radiolabeled with Ga-68 is administered to patients following verification of standard quality controls including activity measurement, pH, radiochemical purity, and visual inspection

Ga-68-PSMA-11

Timothy J Hoffman, PhD

The purpose of this study is to provide access to Ga-68-PSMA-11 PET for evaluation of male veterans with newly diagnosed or biochemically recurrent prostate cancer. All patients will receive conventional imaging (MRI, CT, and/or a molecular imaging bone scan) as well as Ga-68-PSMA-11 PET in order to evaluate the utility of diagnostic testing in patients with positive PSA status, a comparison of results from conventional imaging and PSMA PET imagining will be performed.

Participants (male veterans) with initial diagnosis of prostate cancer or biochemically recurrent disease that consent to participate in the study will receive both conventional imaging (MRI, CT, and/or molecular imaging bone scan) as well as Ga-68-PSMA-11 PET/CT. Following baseline assessment (Visit #1), Ga-68-PSMA-11 (3-7 mCi) will be administered as a single intravenous administration with PET/CT performed approximately 60 minutes after injection (Visit #2A). At approximately 120 minutes after injection of Ga-68-PSMA-11, the final evaluation for safety and tolerability will occur (Visit #2B)

All eligible and consenting participants (male veterans) will receive a single administration of 3-7mCi Ga-68-PSMA-11 per enrollment in addition to conventional imaging (MRI, CT, and/or molecular imaging bone scan).

Male Veterans over the age of 18 years with previously diagnosed prostate cancer

Ga-68-PSMA-11 in Men With Prostate Cancer

Utility of Ga-68-PSMA-11 in Management of Prostate Cancer

A de-identified, anonymized dataset will be prepared to share with other VA investigators upon request

Localized vs extra-pelvic recurrence will be determined for each patient based on Ga-68-PSMA-11 PET/CT and standard-of-care radiological imaging

Harry S. Truman Memorial Veterans' Hospital

University of Missouri-Columbia

Telix Pharmaceuticals, Ltd

Timothy Hoffman

Research Career Scientist

Testosterone

Darolutamide treatment arm is single cohort in lead-in phase.

The conduct of the randomized phase is dependent on the results of the lead-in phase.

Darolutamide(BAY1841788, Nubeqa)

Enzalutamide

Researchers are looking for a better way to treat men who have biochemically recurrent hormone-naïve prostate cancer.

Hormone-naïve prostate cancer is a prostate cancer that has not yet been treated with hormonal therapy including androgen deprivation therapy (ADT). Biochemically recurrence (BCR) means that patients who received local treatment (surgery or radiation therapy) for prostate cancer now present with a rise in the blood level of a specific protein called PSA (prostate-specific antigen) but no detectable cancer or cancer spreading after a treatment that aimed to cure their prostate cancer (e.g. surgery and radiation). This may mean that the cancer has come back as the PSA level can be taken as a marker for prostate cancer development. Although men with BCR may not have symptoms for many years, proper treatment for BCR is important as the cancer may spread to other parts of the body in 7-8 years.

In prostate cancer patients, male sex hormones like testosterone (also called androgens) can sometimes help the cancer spread and grow. To reduce androgen levels in these patients, androgen deprivation therapy (ADT) is often used.

Second generation androgen receptor inhibitors including Darolutamide and Enzalutamide are available for the treatment of prostate cancer in addition to ADT. These inhibitors work by blocking androgen receptors and preventing it from attaching to proteins in cancer cells in the prostate. It is already known that men with prostate cancer benefit from these treatments. But besides benefits, Darolutamide and Enzalutamide are not without side effects.

Clinical studies have shown that treatment with Enzalutamide increase testosterone level in serum, probably because it can pass blood brain barrier and goes into the central nervous system (CNS). The increased testosterone levels are thought to cause some specific side effects including so called feminizing side effects like overdevelopment of the breast tissue in men, and breast tenderness. Darolutamide has a distinct chemical structure and reduced ability to enter the CNS compared with Enzalutamide. That means that Darolutamide potentially leads to fewer and less severe side effects than Enzalutamide.

In this study researchers will collect more data to learn to what extent Darolutamide affects serum testosterone levels in men with BCR in hormone-naïve prostate cancer. This study will consist of 2 stages. In stage 1 (also called lead-in phase) all participants will take Darolutamide by mouth twice a day. The study team will monitor and measure testosterone levels in the blood after:

* 12 weeks
* 24 weeks and
* 52 weeks of treatment.

The second stage (also called randomized phase) is conditional and depends on the results from the stage 1. It will be conducted if after 24 weeks of treatment with Darolutamide in stage 1:

* a mean change in blood testosterone levels is below 45% and
* if the feminizing side effects (including overdevelopment of the breast tissue in men, and breast tenderness) will occur less frequently than previously reported.

In the second stage of this study all participants will be randomly (by chance) assigned into two treatment groups, taking either Darolutamide twice daily or Enzalutamide once daily by mouth for a minimum of 12 and a maximum of 52 weeks.

During both stages of this study the study team will:

* do physical examinations
* take blood and urine samples
* examine heart health using ECG
* examine heart and lung health using CPET
* check bone density using x-ray scan (DEXA)
* check vital signs
* check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan
* ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

The study participants who receive Darolutamide in stage 2 can continue to receive their treatments as long as they benefit from the treatment. The participants from the Enzalutamide group can also switch to treatment with Darolutamide after finishing stage 2. The study team will continue to check the participants' health and collect information about medical problems that might be related to Darolutamide until up to 30 days of last dose for those participants who continue on treatment with Darolutamide.

A Study Called ARAMON to Learn to What Extent Does Study Treatment With Darolutamide Affects Testosterone Levels in Men With Prostate Cancer That Had Not Been Treated With Hormonal Therapy Compared to Treatment With Enzalutamide

A 2-stage, Lead-in and Randomized, Phase 2, Open-label Study of Darolutamide Versus Enzalutamide as Monotherapy on Testosterone Levels Change in Men With Hormone-Naïve Prostate Cancer

AE assessments using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0

QoL assessment using Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P) questionnaire. FACT-P is a multidimension, selfreport QoL instrument specifically designed for patients with prostate cancer. It consists of 39 questions items, made up by 2 parts: the 27 questions for functional assessment of cancer therapy general (FACT-G) and 12 prostate cancer subscale questions. It assesses 4 main domains which are: physical (n=7), social/family (n=7), emotional (n=6) and functional wellbeing (n=7).

Anti-Infective Agents

Antirheumatic Agents

Hydroxychloroquine

Itraconazole

Hydroxyitraconazole

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Suba-itraconazole in combination dose escalating hydroxychloroquine H

Suba-itraconazole with recommended phase II dose of hydroxychloroquine as determined by phase I arm.

SUBA-itraconazole

Anthony Joshua, MBBS(Hons) PhD

Recent pre-clinical work has suggested that Itraconazole has an anti-cancer effect that works synergistically with hydroxychloroquine. This may delay the need for androgen deprivation therapy (ADT) and its associated toxicities in men with biochemically recurrent (BCR) prostate cancer. This study aims to determine feasibility, safety and efficacy of suba-itraconazole (SI) in combination with hydroxychloroquine (HQ) in the treatment of biochemically recurrent (BCR) prostate cancer as means of delaying time to commencement of androgen deprivation therapy.

A rising PSA following treatment with definitive prostatectomy or radiation therapy for localised prostate cancer represents biochemical relapse (BCR), a disease state for which there is no consensus on optimal management. A proportion of men with BCR will go on to develop metastatic disease but there may be a prolonged period of time between biochemical recurrence and overt clinic progression. Though androgen deprivation therapy (ADT) may prolong metastasis-free survival, it comes at a cost of significant morbidity. Thus substantial efforts are underway to find treatments that may delay the need for ADT while maintaining quality of life in men with BCR prostate cancer.

Autophagy inhibitors given in combination with cytotoxic agents have been found to suppress tumour growth and trigger cell death to a greater extent than chemotherapy alone, both in vitro and in vivo. Such inhibitors include the anti-malarial drug chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ). Taken together, autophagy may represent a major mechanism for treatment resistance and thus, represents a potential novel therapeutic target. Moreover, hydroxychloroquine has shown modest activity as a single agent in men with BCR prostate cancer.

The antifungal drug itraconazole has shown some activity in prostate cancer. These effects are attributed to inhibitory effects on endothelial cell proliferation and angiogenesis, mTOR inhibition through effects on intracellular cholesterol trafficking, hedgehog pathway inhibition and induction of autophagy. With regards to cholesterol trafficking, itraconazole causes depletion of plasma membrane cholesterol and cholesterol trapping in the late endosomes and lysosomes in part through inhibition of the cholesterol transporter NPC1.

Pre-clinical studies have shown enhanced death of prostate cancer cells with treatment of itraconazole combined with hydroxychloroquine. This treatment causes a dramatic increase in the accumulation of free cholesterol with a phenotype reminiscent of Niemann-Pick Syndrome, a neurodegenerative disease characterised by accumulation of free cholesterol in late endosomes/lysosomes due to mutations in NPC1 and NPC2. The investigators hypothesise that itraconazole synergises with hydroxychloroquine to induce sequestration of cholesterol in the lysosomes while inhibiting autophagy thereby inducing cell death through oxidation of the excess cholesterol and cell dysfunction as a result of the inaccessibility of the cholesterol. This mechanism may be particularly potent in androgen sensitive prostate cancer where cholesterol use is destined for androgen synthesis.

Non-castrating treatments for BCR and metastatic prostate cancer are an area of unmet need. The aim of this study is to assess the tolerability, safety and efficacy of hydroxychloroquine in combination with itraconazole as a strategy to delay time to ADT commencement in men with BCR prostate cancer.

Phase I intra-patient dose escalation study Phase II Simon 2-stage cohort expansion

Phase I/II Study of Hydroxychloroquine With Itraconazole With Biochemically Recurrent Prostate Cancer

A Phase I/II Study of Hydroxychloroquine and Itraconazole as Therapy for Men With Androgen Normalised Prostate Cancer

Rate of adverse events defined by CTCAE criteria

Time from commencement of treatment to first metastatic lesion on CT or WBBS

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
[Ac-225]-PSMA-62 Trial in Biochemically Recurrent and Metastatic Castration Resistant Prostate Cancer	NCT06229366	Prostate Cancer Metastatic Cast... Biochemically R...	[Ac-225]-PSMA-6... [Ac-225]-PSMA-6...	18 Years -	POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies	NCT05794906	Biochemically R...	Darolutamide (B... Placebo matchin... ADT	18 Years -	Bayer
[Ac-225]-PSMA-62 Trial in Biochemically Recurrent and Metastatic Castration Resistant Prostate Cancer	NCT06229366	Prostate Cancer Metastatic Cast... Biochemically R...	[Ac-225]-PSMA-6... [Ac-225]-PSMA-6...	18 Years -	POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
Ga-68-PSMA-11 in Men With Prostate Cancer	NCT05744115	Prostate Cancer Prostate Adenoc...	Ga-68-PSMA-11	18 Years -	Harry S. Truman Memorial Veterans' Hospital
A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies	NCT05794906	Biochemically R...	Darolutamide (B... Placebo matchin... ADT	18 Years -	Bayer
A Study Called ARAMON to Learn to What Extent Does Study Treatment With Darolutamide Affects Testosterone Levels in Men With Prostate Cancer That Had Not Been Treated With Hormonal Therapy Compared to Treatment With Enzalutamide	NCT05526248	Biochemically R...	Darolutamide(BA... Enzalutamide	18 Years -	Bayer
Phase I/II Study of Hydroxychloroquine With Itraconazole With Biochemically Recurrent Prostate Cancer	NCT03513211	Prostate Cancer	SUBA-itraconazo... Hydroxychloroqu...	18 Years -	St Vincent's Hospital, Sydney

Spots Global Cancer Trial Database for biochemically recurrent prostate cancer