Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Abiraterone Acetate

Patients initiating novel hormonal therapy (abiraterone, apalutamide or enzalutamide) for mCSPC

Novel hormonal therapy

Pfizer CT.gov Call Center

The purpose of this study is to learn about how long novel hormonal therapies are taken by men to treat mCSPC. Novel hormonal therapies in this study include study medicines abiraterone, apalutamide, and enzalutamide.

Prostate cancer is one of the most common cancers in men. The prostate is a gland in the male body that helps make semen. Metastatic cancer is a cancer that has spread to other parts of the body. Castration-sensitive prostate cancer means the cancer is being controlled by keeping the testosterone levels as low as would be expected if the testicles were removed by surgery.

This is a real-world study, not a clinical trial. This means that researchers will look at what happens when men receive the treatments prescribed by their own doctor as part of their usual healthcare treatment. In this study, researchers will use insurance claim information from Medicare claims data.

The study will include patients' information from the database for men who:

* Were identified to have mCSPC.
* Started treatment with novel hormonal therapy (index date) for mCSPC.
* Were 65 years of age or older one year before index date.

Men in this study will be taking novel hormonal therapy for treatment of their mCSPC. We will describe how long men take novel hormonal therapy. This study will use patient information from insurance claims. It will take information one year before start of novel hormonal treatment until the end of insurance period or until information is available.

A Study to Learn About Novel Hormonal Therapies in People With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Novel Hormonal Therapies (NHTs) for the Treatment of Metastatic Castration-sensitive Prostate Cancer (mCSPC) in the Medicare Population

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Treatment duration will be defined as the time from the initiation of novel hormonal therapy (abiraterone, apalutamide, or enzalutamide) to the discontinuation date. Discontinuation will be defined as the earliest of 1) death, 2) last observed pharmacy claim plus days of supply associated with last claim, 3) day before the start of next line of therapy, or 4) end of data availability.

Astellas Pharma Inc

Pfizer

Pharmaceutical Solutions

Anti-Inflammatory Agents

Androgens

Carboplatin

Niraparib

Docetaxel

Prednisone

Taxane

Poly(ADP-ribose) Polymerase Inhibitors

Radium Ra 223 dichloride

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.

Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.

Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.

DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.

Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.

Patients with alterations in the PI3K pathway will have an increased chance of receiving the combination treatment with Capivasertib plus Docetaxel.

Only patients with DNA-repair deficiency will be treated with Carboplatin as second line treatment in the castration-resistant phase of ProBio.

Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics).

Enzalutamide Oral Capsule

Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC.

Abiraterone Oral Tablet

Carboplatin will be administered every 3rd week with an AUC (area under curve) = 5 with a dose calculated according to the Carboplatin AUC Dose calculation (Calvert formula):Dose (mg) = TargetAUC (mg/ml x min) x \[GFR ml/min + 25\].

Cabazitaxel 60 mg Solution for Injection

Docetaxel Injectable Solution

Radium Chloride Ra-223

Niraparib and Abiraterone acetate will be provided by Janssen and will be provided either as a fixed dose combination or as single agents. Detailed use of the study treatment including dose and dosages are described in the Investigator's brochures and SmPC.

Niraparib plus Abiraterone acetate plus Prednisone

Capivasertib is provided by AstraZeneca and will be given in combination with Docetaxel. All subjects will be given up to ten 21-day docetaxel cycles. All subjects will receive Capivasertib, which will be administered as tablets taken twice a day orally, on a 4 days on/3 days off continuous schedule, commencing cycle one, day 2, until disease progression.

Capivasertib plus Docetaxel

Apalutamide

Darolutamide

Berit Larsson, MSc

Henrik Grönberg, Professor

Bram De Laere, PhD

Peter Schatterman, MD

Michiel Strijbos, MD, PhD

Christophe Ghysel, MD

Daan De Maeseneer

Wendy De Roock, MD

Caroline Verbaeys, MD, PhD

Piet Ost, Prof. dr.

Daisy Luyten, MD

Siska Van Bruwaene

Brieuc Sautois, MD

Jochen Darras, MD

Els Everaert, MD, PhD

Maria Persson, RN

Christoph Müller, MD, PhD

Jan Oldenburg, Prof. dr

Maria N Vigmostad, MD, PhD

Hege S Haugnes, Prof, dr

Bjorg Y Aksnessaether, MD PhD

Ingrida Verbiéne, MD, PhD

Susanne Johansson, B.Sc.

Christine Jaredsson, MD, PhD

Linn Pettersson, MD, PhD

Mats Andén, MD, PhD

Johan Sandzen, MD, PhD

Anders Ullén, MD, PhD

Marie Hjälm Eriksson, MD PhD

Elin Jänes, MD PhD

Camilla Thellenberg Karlsson, MD PhD

Gunilla Enblad, Professor

Ingela Franck Lissbrant, MD, PhD

Martha Olsson, MD, PhD

Jenny Kahlmeter Brandell, MD, PhD

Arnoud Templeton, MD

Ashkan Mortezavi, MD PhD

Martin Eklund, Professor

Johan Lindberg, PhD

Piet Ost, Professor

Jan Oldenburg, Professor

Ashkan Mortezavi, MD, PhD

ProBio is an international, outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic prostate cancer. Patients will be randomized to control or experimental treatment arms. Patients in the control arm will receive standard of care following national guidelines. Patients in the experimental arm will be randomized to treatments based on a biomarker signature inferred from diagnostic tissue or liquid biopsy profiling. The predefined biomarker signatures are tumor properties or mutations in genes/pathways with previously demonstrated clinical validity (e.g. prognostic value or association with treatment response). The biomarker signatures are identified using a hybridisation capture gene panel specifically designed for prostate cancer.

ProBio is an outcome-adaptive, multi-arm, open-label, multiple assignment randomised biomarker driven platform trial in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

Patients will be randomised to control or experimental treatment class arms. Patients in the control arm will receive standard of care following national guidelines and will remain within the control arm throughout the course of the trial. Patients in the experimental arm will be randomised to a treatment class (consisting of one or multiple drugs) based on a biomarker signature. The biomarker signatures are defined as tumour properties or mutations in certain genes/pathways identified in the scientific literature as important in prostate cancer treatment response. The biomarker signatures are identified using a gene panel specifically designed for advanced prostate cancer.

Alterations in the following genes/pathways or combinations thereof constitute the biomarker signatures:

* Androgen receptor
* DNA-repair deficiency
* TP53
* TMPRSS2-ERG gene fusion
* PI3K pathway alterations

Patients in the experimental arm can be randomized to the following treatments classes:

for mHSPC

* AR signalling inhibitors (Abiraterone acetate, Enzalutamide, Apalutamide)
* Taxane-based chemotherapy in combination with ARSi (Docetaxel plus Abiraterone acetate, or Darolutamide)
* PolyADP Ribose Polymerase Inhibitors (Niraparib plus Abiraterone Acetate)

for mCRPC

* AR signalling inhibitors (Enzalutamide, Abiraterone acetate)
* Poly ADP Ribose Polymerase Inhibitors (Niraparib plus Abiraterone acetate)
* Selective AKT Inhibitor (Capivasertib plus Docetaxel)

ProBio will use outcome-adaptive randomization, adapting the randomization based on the observed progression free survival (PFS) within biomarker signatures. Treatments will initially be assigned to patients based on the biomarker signatures for which that treatment is most likely to be effective. The trial will be analyzed within a Bayesian framework, which allows for calculations of the probability for each treatment that it is superior to standard of care within a given signature. Each experimental arm will be evaluated for efficacy relative to the control arm with the same biomarker signatures.

Participants and treating physicians will be blinded to ctDNA profile of each patient. The biomarker signatures will thus not influence treatment choice among controls (reflecting today's standard of care).

Further, ProBio will use the sequential multiple assignments trial (SMART) concept, where each patient who progresses within the trial will re-enter the trial and be re-assigned to another treatment based on the patient's current ctDNA profile. Patients will be withdrawn after in total maximal three randomized consecutive treatments after inclusion into the study.

The randomization probabilities within the experimental arm are defined in proportion to the probability that each treatment is superior to standard of care within a given biomarker signature, and therefore change as data accumulates in the trial and knowledge accumulates for what biomarker signatures and specific treatments that are more probable to be effective.

Trial results will be evaluated regularly by an independent data and safety monitoring board (DSMB). The DSMB will evaluate treatment-signature combinations with respect to:

* Graduation for superiority: A treatment-biomarker signature combination will be graduated from the trial if it has a Bayesian predictive probability of success in a future confirmatory phase III trial exceeding a pre-specified threshold (85%).
* Termination for futility: Treatment-biomarker signature combinations will be dropped from the trial for futility when success probabilities drop sufficiently low (less than 10% using a minimum of 20 patients assigned to the specific treatment-biomarker signature combination).
* Alternatively, if the maximum sample size of 300 and 150 patients (for mHSPC and mCRPC, respectively) assigned to a treatment biomarker signature is reached without graduation for superiority, assignments to that combination will end.

ProBio is a platform study. This means that new treatments and biomarker signatures can be added to the experimental arm in the future. This will be done after protocol amendments.

ProBio will use outcome-adaptive randomization, adapting the randomization based on the observed PFS within biomarker signatures. Treatments will initially be assigned to patients based on the biomarker signatures for which that treatment is most likely to be effective. The trial will be analysed within a Bayesian framework, which allows for calculations of the probability for each treatment that is superior to standard of care within a given signature. Each experimental arm will be evaluated for efficacy relative to the control arm with the same biomarker signatures.

ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer

ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Prostate Cancer

Progression will be evaluated by the established international standards of the Prostate Cancer Working Group version 3 (PCWG3) and for soft tissue metastases (e.g. lung, liver and lymph nodes) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1).

Time to development of castration-resistance, as defined by EAU guidelines (biochemical progression or radiologic progression)

Treatment response is evaluated according to PCWG3 and RECIST 1.1

OS is defined as time to death from any cause (overall and prostate cancer specific)

QoL will be assessed using the EORTC QLQ-C30 instrument

Cost effectiveness will be assessed by using the EQ-5D-5L instrument to estimate health utilities. Treatment costs will be based on drug costs and reimbursement data.

Common Terminology Criteria for Adverse Events (CTCAE) developed and maintained by the US National Cancer Institute will be used to record adverse events

Response rates at 6 months on therapy will be evaluated by the established standards of EAU Guidelines

The Swedish Research Council

Kom Op Tegen Kanker

Janssen Pharmaceutica N.V., Belgium

AstraZeneca

Cancerfonden

Karolinska Institutet

Professor of Cancer Epidemiology

Symptoms and General Pathology

Rare Diseases

Disease Progression

Kennedy Disease

Gallium 68 PSMA-11

Pluvicto

Radiopharmaceuticals

Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

administered intravenously once every 6 weeks (1 cycle) for 6 cycles

177Lu-PSMA-617

Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD

68Ga-PSMA-11

Administered orally on a continuous basis as per package insert and guideline

ARDT

ADT are administered as per physician order

Novartis Pharmaceuticals

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants have been enrolled in 20 countries.

In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.

The randomization will be stratified according to the following three factors: disease volume (high v low), age \>= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.

Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD.

Prior treatment:

* Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
* Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.

Randomization period:

The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

Participants from both arms will also undergo PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =\< 7 days and enter the Post-treatment Follow-up .

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Patient randomized to SOC arm have an option to crossover to 177Lu-PSMA-617 treatment after rPFS

An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC

An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

rPFS is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

OS is defined as time to death for any cause

PSA90 response is defined as the proportion of patients who have a more/equal 90% decrease in PSA from baseline, it will be calculated at 12, 24 and 48 months

Time to development of mCRPC is defined as the time from date of randomization to disease progression despite androgen deprivation therapy (ADT) presenting as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre existing disease, and/or the appearance of new metastases.

PFS is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first

PFS2 is defined as time from date of randomization to the first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) on next-line therapy or death from any cause, whichever occurs first.

Proportion of patients with PSA \< 0.2 ng/mL at months 12, 24 and 48 months

TTSTP is defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as assessed by Blinded Independent Central Review (BICR)

Time to SSE (TTSSE) is defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first

ORR is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DCR is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR).

FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT-General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

The distribution of adverse events (AE) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Alliance Foundation Trials, LLC.

RTOG Foundation, Inc.

Cohort A:150 patients with high risk localized prostate cancer (defined as \>cT3 or PSA \> 20 ng/mL or presence of ECE or SVIat mpMRI), with tissue available from diagnostic biopsy/prostatectomy undergoing or who underwent curative treatment (prostatectomy/radical radiotherapy) but have not started a FU pathway.

Patients within Cohort A will be followed up with PSA every 3 months for 3 years and early scans. They will also receive a blood sample for ctDNA/CTC before (when feasible) and after radical treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression

Cohort B: 100 patients with de novo metastatic hormone sensitive prostate cancer (mHSPC) with tissue available from diagnostic biopsy of the primary and when possiblepossible, from a metastatic site. Patients must either have not started a standard treatment or have started for not longer than 3 months;Patients within Cohort B will be followed up with PSA and scans every 3 months. They will also receive a blood sample before (when feasible) or after the start of systemic treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression

Cohort C:100-150 patients with metastatic castration resistant prostate cancer tissue (mCRPC) progressing on a standard treatment with available from biopsy of a metastatic site, and when possiblepossible, from the primary.Patients within Cohort C will be followed up with PSA monthly and scans every 3 month. They will also receive a blood sample for ctDNA/CTC before (when feasible) or after the start of systemic treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression.

ilaria Buondonno, PhD

Marco Asioli

Pasquale Rescigno, MD

Ilaria Buondonno, PhD

Francesco Porpiglia, MD

400 patients will be enrolled and divided into 3 cohorts: Cohort A: patients with high risk localized prostate cancer (PC) defined as \>cT3 or PSA \> 20 ng/mL or presence of ECE or SVI at mpMRI;

Cohort B: patients with de novo metastatic hormone sensitive prostate cancer (mHSPC);

Cohort C: patients with metastatic castration resistant prostate cancer (mCRPC) progressing on a standard treatment.

In this study 150 patients will be enrolled in cohort A, 100 patients in cohort B and 100-150 patients in Cohort C.

Considering the known frequency of DDR and MMR germline/somatic alterations, it is expected to see:

* 15-23 patients with germline/somatic DDR defects and 5-7 MMR alterations in cohort A;
* 20-25 patients with germline/somatic DDR defects and 5-7 MMR alterations in cohort B;
* 25-35 patients with germline/somatic DDR defects and 7-10 MMR alterations in cohort C.

Patients within Cohort A will be followed up with PSA every 3 months for 3 years and early scans. They will also receive a blood sample for ctDNA/CTC before (when feasible) and after radical treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression;

Patients within Cohort B will be followed up with PSA and scans every 3 months. They will also receive a blood sample before (when feasible) or after the start of systemic treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression.

Patients within Cohort C will be followed up with PSA monthly and scans every 3 month. They will also receive a blood sample for ctDNA/CTC before (when feasible) or after the start of systemic treatment, 6 months and 12 months (if not progressed), at time of PSA or radiological progression.

will be collected: one test tube of ctDNA before the radical biomedical treatment, one will be collected after 6 and 12 months and at the time of progression. A representative sample of archival tumor tissue from diagnostic biopsy/prostatectomy and a biopsy of the metastasis will also be collected

INSIDE: Identification of Genomic Screening Pathways in Cancer Patients With DNA Repair Alterations

Identification of Genomic Screening Pathways in Cancer Patients With DNA Repair Alterations

Evaluation of the frequency, number and type of DDR and MMR germline/somatic alterations in the study population

Evaluation of PSA levels (baseline versus follow-up) in the 3 cohorts compared with radiological assessment

Number of patient-derived preclinical models (primary 2D cell lines, organoids or PDXs)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Learn About Novel Hormonal Therapies in People With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)	NCT06072196	Prostatic Neopl...	Novel hormonal ...	65 Years -	Pfizer
ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer	NCT03903835	Metastatic Cast... Metastatic Horm...	Enzalutamide Or... Abiraterone Ora... Carboplatin Cabazitaxel 60 ... Docetaxel Injec... Radium Chloride... Niraparib plus ... Capivasertib pl... Apalutamide Darolutamide	18 Years -	Karolinska Institutet
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
INSIDE: Identification of Genomic Screening Pathways in Cancer Patients With DNA Repair Alterations	NCT06334809	Prostate Cancer		18 Years -	Fondazione del Piemonte per l'Oncologia
An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC	NCT04720157	Prostatic Neopl...	177Lu-PSMA-617 68Ga-PSMA-11 ARDT ADT	18 Years -	Novartis
A Study to Learn About Novel Hormonal Therapies in People With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)	NCT06072196	Prostatic Neopl...	Novel hormonal ...	65 Years -	Pfizer

Spots Global Cancer Trial Database for mhspc

Every month we try and update this database with for mhspc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mhspc

Every month we try and update this database with for mhspc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mhspc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.