Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Diseases and Abnormalities at or Before Birth

Prostatic Neoplasms

Congenital Abnormalities

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Docetaxel

Abiraterone Acetate

Prednisone

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).

Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.

Abiraterone acetate or Enzalutamide or Docetaxel

The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.

A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by zr pharma\& Austria GmbH

The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).

Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).

The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).

Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).

Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive.

Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive.

ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).

CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.

Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.

Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria.

Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria.

Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P total score, on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (ie more negative) from baseline to week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.

Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (BPI-SF) questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.

Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L VAS; on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.

Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints week 5, 9, 13 and 17; only Week 5 data presented.

Foundation Medicine

pharmaand GmbH

After 28 days following last dose of study drug, only SAEs assessed as potentially related to study drug are reported. Events of progression of the participant's underlying cancer as well as events clearly related to progression of the participant's cancer (signs and symptoms of progression) and progression of disease leading to death are not reported as an AE or SAE.

Oral rucaparib (monotherapy).

Rucaparib: Rucaparib will be administered daily.

Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).

Abiraterone acetate or Enzalutamide or Docetaxel: Abiraterone acetate and enzalutamide will be administered daily.

Docetaxel will be administered every 3 weeks.

Abiraterone Acetate or Enzalutamide or Docetaxel

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

North America

Europe

Australia

Israel

Region of Enrollment

Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status Scale. ECOG 0 = Fully active, able to carry on all pre-disease performance without restriction. ECOG 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work or office work)

ECOG Performance Status (at stratification)

Gene Alteration (at stratification)

Baseline prostate specific antigen (PSA)

The scale for the Gleason score ranges from 2 to 10, with higher scores indicating a worse prognosis

Gleason score ≥8 at diagnosis

Measurable Disease per Independent Radiological Review (IRR)

Bone

Nodal

Visceral

Participants may be counted in more than one category

Metastases site(s) by IRR

Prior Therapies for CRPC

Abiraterone acetate

Apalutamide

Enzalutamide

Docetaxel for hormone-sensitive prostate cancer

Prior therapy (2nd generation androgen receptor pathway inhibitor (ARPI) or docetaxel only)

Intent-to-Treat (ITT) Population included all randomized participants (participants with breast cancer gene \[BRCA\] mutated metastatic castration-resistant prostate cancer \[mCRPC\] and participants with ataxia- telangiectasia mutated serine/threonine kinase \[ATM\] mutated mCRPC).

Medical Information Department

Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration

ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC).

Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined

Interim Overall Survival in Participants With a BRCA Alteration

Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined

ITT Population with BRCA mutated mCRPC and measurable disease at baseline.

Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration

ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC) with measurable disease at baseline.

Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined

ITT Population with BRCA mutated mCRPC and measurable disease at baseline. 'Overall number of participants analyzed' = participants with objective response.

Duration of Response (DOR) by IRR in Participants With a BRCA Alteration

ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC) with measurable disease at baseline. 'Overall number of participants analyzed' = participants with objective response.

Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined

PSA Response in Participants With a BRCA Alteration

PSA Response in Participants With a BRCA or ATM Alteration Combined

The Safety Population included all participants with BRCA mutated mCRPC who received at least one dose of protocol-specified treatment and had 6 months of follow-up prior to the data cutoff.

Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration

The Safety Population included all participants who received at least one dose of protocol-specified treatment and had 6 months of follow-up prior to the data cutoff.

Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined

Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration

Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined

ITT Population with BRCA mutated mCRPC. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P

BPI-SF Pain Score

BPI-SF Interference Score

ITT Population with BRCA mutated mCRPC. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L

Safety Population with at least 1 PK sample collected.

Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling

Treatment Phase

Cross-Over Phase

Symptoms and General Pathology

Nervous System Diseases

Heart and Blood Diseases

Nutritional and Metabolic Diseases

Immune System Diseases

Rare Diseases

Neoplasm Metastasis

Recurrence

Ataxia

Cerebellar Ataxia

Telangiectasis

Ataxia Telangiectasia

Disease Attributes

Subjects will receive a single dose of XRD-0394 capsules approximately 90 minutes before RT on Day 2 of the RT regimen

Subjects will receive a single dose of XRD-0394 capsules approximately 90 minutes before RT. A single biopsy will be performed in each subject (either after RT alone or after XRD-0394 and RT).

XRD-0394

Palliative radiotherapy

XRD-0394 is a novel, potent, oral, small molecule dual inhibitor of ataxia telangiectasia mutated kinase (ATM) and deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK) that has selectivity compared with other phosphatidylinositol 3-kinase-related kinase (PIKK) family enzymes. This is a first-time-in-human study, which means that it is the first time the study drug is being used in humans. The purpose of the study is to evaluate the safety and tolerability of single doses of XRD-0394 administered with palliative radiotherapy (RT) to subjects with metastatic, locally advanced, or recurrent cancer. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of single-dose XRD-0394 administered in combination with palliative RT will also be characterized.

This is a Phase 1, multicenter, open-label, dose-finding, PK and PD study of XRD-0394 in subjects with metastatic, locally advanced, or recurrent cancer receiving palliative RT. The study will evaluate single-dose PK of XRD-0394 administered to serial cohorts of subjects with the intent of identifying an oral dose that achieves plasma drug concentrations within a specified therapeutic range. Once target plasma concentrations of XRD-0394 are reached, one or more PD cohorts of subjects will be enrolled in order to demonstrate inhibition of radiation-induced ATM activity in tumor biopsy samples from subjects who received the selected dose(s).

Single Dose Escalation: Eligible subjects will be enrolled in serial cohorts to evaluate the PK of single ascending doses of XRD-0394. Dose escalation of XRD-0394 will proceed based on a standard 3+3 design. The starting dose of XRD-0394 will be 40 mg, followed by planned doses of 80 mg and 160 mg. Following administration of a single-dose of XRD-0394 and completion of RT, subjects will be evaluated for the occurrence of dose-limiting toxicities (DLTs). The available PK and safety data for each cohort will be reviewed at the conclusion of the DLT evaluation period before the decision to escalate to the next dose is made. The evaluation of additional doses of XRD-0394 will be determined based on the safety and PK data collected at completed dose levels. Dose escalation may continue until the objectives of the study are met and/or the maximum tolerated dose (MTD) of XRD-0394 is reached. PK samples for measurement of plasma concentrations of XRD-0394 will be collected pre-dose and at specified time points following XRD-0394 administration. Safety and tolerability of each XRD-0394 dose level will be evaluated by assessment of treatment-emergent adverse events (TEAEs), DLTs, and discontinuations due to TEAEs. A Safety Monitoring Committee (SMC) will be used during the study to monitor subject safety and evaluate potential DLTs.

Pharmacodynamic Assessment: The dose identified to produce plasma drug concentrations of XRD-0394 within a targeted therapeutic range will be further evaluated in separate PD cohort(s) of subjects. Subjects enrolled in a PD cohort must have a target tumor with a soft tissue component that is accessible for biopsy and must agree to undergo 1 biopsy during their RT regimen. PK samples for measurement of plasma concentrations of XRD-0394 will be collected from all subjects at pre-dose and at specified time points after XRD-0394 administration. Safety and tolerability of XRD-0394 will be evaluated by assessment of TEAEs.

Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients

A Phase 1, Open-Label, Dose-Finding, Pharmacokinetic, and Pharmacodynamic Study of XRD-0394 in Subjects With Metastatic, Locally Advanced, or Recurrent Cancer Receiving Palliative Radiotherapy

XRad Therapeutics Inc

The exposition to the primary analysis risk factor (germline deleterious mutation in BRCA1, BRCA2, ATM or PALB2 gene) will be determined after inclusion. Briefly, a NGS targeted-panel based on the majority of genes included in the BROCA panel and additional DNA-repair related genes has been designed based on the available technology. The pathogenicity of germline variants will be determined according to established American College of Medical Genetics and Genomics and Association for Molecular Pathology current consensus at the time of final primary outcome analyses. Variants will also be reviewed against published literature and public databases. According to their mutation-carrier status patients will be classified as: A) Mutation Carriers in BRCA1, BRCA2, ATM and PALB2 genes; B) Mutation carriers in other genes included in the BROCA panel; C) Mutation carriers in others DNA-repair genes D)Non-carriers

David Olmos, MD

PROREPAIR is a prospective multicenter observational cohort study of unselected patients with metastatic Castration Resistant Prostate Cancer (mCRPC) with unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent.

The study aims to evaluate the impact of aberrations in DNA-repair genes,(BRCA1, BRCA2, ATM and PALB2 and other genes) on cause-specific survival from the diagnosis of the metastatic castration resistant status and other outcomes.

This is a non-interventional study in which eligible patients are prospectively followed-up until death or the end-of-study, whichever happens first.

Patients are enrolled after mCRPC diagnosis and before or within the 6 first months of starting a first-line treatment with any approved survival-prolonging agent for mCRPC. First and subsequent treatment lines will be chosen according to the patients and their treating physicians preferences and will not be dictated by this study.

A whole blood sample for germline DNA extraction as well as any available archival prostate cancer tissue samples will be collected at baseline. Optional plasma, serum and whole blood samples will be collected at baseline and at different time points along the evolution of the disease. A sample will be collected within the last 6 months of life.

Survival and treatment outcomes including biochemical, radiological and clinical progression with standard approved agents abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223 will be prospectively collected.

Primary aim is to evaluate the prevalence and impact of DNA repair germline mutations in the BRCA1, BRCA2, ATM and PALB2 genes on cause-specific survival from mCRPC. Secondary aims will include the correlation of additional germline alterations in DNA-repair with survival and treatment outcomes; the analyses of the survival and treatment outcomes impact of somatic alterations in these genes and the role of germline and somatic defects in the clonal evolution of prostate cancer.

Whole blood, plasma, serum, archival FFPE and fresh tumour samples

Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)

Prospective Multicentre Cohort Study of the Prevalence and Clinical Impact of Germline Deleterious Mutations in DNA Repair Genes of Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

To assess the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations on cause-specific survival from diagnosis of metastatic castration resistance status.

To analyze the impact of other germline mutations in other DNA repair genes on cause-specific survival from diagnosis of metastatic castration resistance

To explore the correlation between DNA repair germline mutation carrier status and cause-specific survival following first, second, third and successive treatment lines.

To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the biochemical response and time to biochemical progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.

To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the radiographic response and time to radiographic progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.

To explore in this cohort the correlation between somatic DNA repair abnormalities with cause-specific survival and other treatment-related outcomes.

To correlate DNA repair somatic and germline alterations with prior prostate cancer history characteristics and established risk factors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency	NCT02975934	Metastatic Cast...	Rucaparib Abiraterone ace...	18 Years -	pharmaand GmbH
Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients	NCT05002140	Metastasis Locally Advance... Recurrent Cance...	XRD-0394 Palliative radi...	18 Years -	XRad Therapeutics Inc
A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency	NCT02975934	Metastatic Cast...	Rucaparib Abiraterone ace...	18 Years -	pharmaand GmbH
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients	NCT05002140	Metastasis Locally Advance... Recurrent Cance...	XRD-0394 Palliative radi...	18 Years -	XRad Therapeutics Inc
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Trial of XRD-0394, a Kinase Inhibitor, in Combination With Palliative Radiotherapy in Advanced Cancer Patients	NCT05002140	Metastasis Locally Advance... Recurrent Cance...	XRD-0394 Palliative radi...	18 Years -	XRad Therapeutics Inc

Spots Global Cancer Trial Database for atm

Every month we try and update this database with for atm 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 atm

Every month we try and update this database with for atm 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 atm 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.