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

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Transitional Cell Carcinoma

Urethral Cancer

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR), is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure).

Plasma were collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1.

Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.

HRD Unknown

Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH \< 10% were considered HRD-negative.

HRD Negative

Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.

HRD Positive

Overall

The study was terminated early based on an interim analysis by the Data Monitoring Committee that demonstrated that ORR did not meet the protocol-defined continuance criteria. There were no confirmed responses observed.

Intent-to-treat Population (ITT) with measurable disease at Baseline - The ITT population includes all patients who received at least 1 dose of rucaparib. One patient each in the HRD negative and HRD positive groups did not have measurable disease at Baseline.

Objective Response Rate (ORR) Per RECIST Version 1.1

Intent-to-Treat population - all patients who received at least 1 dose of rucaparib

Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator

Overall Survival

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

Safety population - all patients who received at least 1 dose of rucaparib and who had at least 1 PK sample collected. The number analyzed at each timepoint includes only those participants who remained on study and with viable samples collected at that timepoint.

Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations

Overall Study

Niraparib

Participants will receive 300 milligram (mg) niraparib (3 capsules\*100 mg) orally once daily.

Participants will receive 300 mg niraparib (3 capsules\*100 mg) orally once daily.

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies.

This is a multicenter and open-label (participants and researchers are aware of the treatment that participants are receiving) study that consists of 4 phases: a Prescreening Phase for biomarker evaluation only, a Screening Phase, a Treatment Phase (Cycle 1 Day 1 and will continue until the study drug is discontinued), a Follow-up Phase (every 3 months after end of treatment visit), and a Long-term Extension Phase (until participants no longer derive benefit from treatment or until further notification on different means of study treatment). Participants will be monitored for safety during the study period, and up to 30 days after the last dose of study drug.

An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

ORR defined as percentage of participants with BRCA DNA-repair anomalies and measurable disease whose best response is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and with no evidence of bone progression per Prostate Cancer Working Group 3 (PCWG3) criteria.

ORR defined as percentage of participants with BRCA deoxyribonucleic acid (DNA)-repair anomalies and measurable disease whose best response is either CR or PR per RECIST 1.1 and with no evidence of bone progression per PCWG3 criteria.

CTC response rate was defined as the percentage of participants with CTC equals to (=) 0 per 7.5 milliliter (mL) blood at 8 weeks post-baseline in participants with baseline CTC greater than (\>) 0.

OS is defined as time from enrollment to death from any cause.

rPFS was defined as time from enrollment to radiographic progression or death from any cause, whichever occurred first. Radiographic progression was evaluated per RECIST 1.1 criteria for soft tissue disease and per PCWG3 criteria for bone disease.

Time to radiographic progression is defined as time from enrollment to radiographic progression or death due to disease progression, whichever occurs first. Disease progression is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Time to PSA progression was defined as time from enrollment to the first date of documented PSA progression based on PCWG3 criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanograms per milliliter (ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks.

Time to SSE was defined as the time from enrollment to first occurrence of one of the following symptomatic skeletal events: tumor-related spinal cord compression, radiation to bone to relieve skeletal symptoms, surgery to bone or need for tumor-related orthopedic surgical intervention, symptomatic or pathologic fracture.

Duration of objective response is defined as time from CR or PR to radiographic progression of disease, unequivocal clinical progression or death, whichever occurs first. Unequivocal clinical progression defined as one or more of following: 1) deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS) to Grade 3 or higher; 2) need to initiate any of following because of tumor progression (even in absence of radiographic evidence of disease): alternative anticancer therapy for prostate cancer, radiation therapy, surgical interventions for complications due to tumor progression.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.

Number of participants with worst toxicity grades for clinical laboratory tests (chemistry and hematology) based on NCI-CTCAE were reported. The chemistry laboratory parameters were: alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatinine increased, gamma glutamyl transferase (GGT) increased and the hematology parameters were: hemoglobin increased, lymphocyte count increased. Grading was done as: Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening).

Janssen Research & Development, LLC

Safety analysis set included all participants who received at least 1 dose of study drug.

Male participants who were over the age of 18 years with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies and who had received prior taxane-based chemotherapy and androgen receptor (AR)-targeted therapy received once daily oral dose of 300 milligrams (mg) niraparib capsules starting Day 1 until disease progression, unacceptable toxicity, death, or termination of the study by the sponsor (up to 52 months).

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
Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma	NCT03397394	Bladder Cancer Urothelial Carc... Metastatic Urot... Renal Pelvis Ca... Ureter Carcinom... Urinary Bladder... Urethra Carcino... Muscle Invasive...	Rucaparib	18 Years -	pharmaand GmbH
An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies	NCT02854436	Prostatic Neopl...	Niraparib	18 Years -	Janssen Research & Development, LLC
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
An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies	NCT02854436	Prostatic Neopl...	Niraparib	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for dna defect

Every month we try and update this database with for dna defect 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 dna defect

Every month we try and update this database with for dna defect 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 dna defect 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.