View clinical trials related to BRCA1 Mutation.
Filter by:This is a two-part, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and anti- tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG.
The purpose of this study is to determine if the experimental treatment with poly-ADP ribose polymerase (PARP) inhibitor, ACE-86225106 is safe, tolerable and has anti-cancer activity in adult patients with advanced solid tumors.
Trial design: Phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 or g/tPALB2 mutation, with 2:1 randomization into Arm A (niraparib + elacestrant) or arm B (niraparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study. Trial population: Patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 or g/tPALB2 mutation, having received at least one prior line of chemotherapy or endocrine-based therapy for irresectable, locally advanced, or metastatic disease (or adjuvant treatment with CDK4/6 inhibitor therapy), with ECOG performance status of 0-2 and life expectancy of > 6 months, with normal bone marrow and kidney functions and no active or newly diagnosed central nervous system (CNS) metastases or symptomatic metastatic visceral disease at risk of life-threatening complications. Interventions: Patients randomized to Arm A will receive 200mg niraparib daily and 400mg elacestrant daily, while patients randomized to Arm B will receive 200mg niraparib daily. Blood tests (hematology, biochemistry) will be performed at the beginning of every cycle, and imaging for tumor assessment (chest and abdominopelvic imaging) as well as QoL assessments will be performed every three months and in case of suspicion of progression/end of study.
This is a single center, phase I/Ib clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib with the DNA methyltransferase (DNMT) inhibitor ASTX727, which is an oral formulation of decitabine with cedazuridine (a cytidine deaminase inhibitor that allows for oral administration). The study population consists of adults with advanced/metastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway (i.e., BReast CAncer gene 1 (BRCA1), BReast CAncer gene 2(BRCA2), Partner And Localizer of BRCA2 (PALB2), ATM, and/or Checkpoint kinase 2 (CHEK2) mutations).
The goal of this interventional clinical trial is to learn about TNG348, a ubiquitin specific peptidase 1 (USP1) inhibitor, alone and in combination with olaparib in patients with BRCA 1/2 mutant or HRD+ solid tumors. The main question[s] it aims to answer are: - to evaluate the safety and tolerability of single agent and combination therapy - to determine the recommended dose for Phase 2 of single agent and combination therapy - to determine the pharmacokinetics of TNG348 as a single agent and in combination therapy - to evaluate the initial antineoplastic activity as a single agent and in combination therapy Participants will receive study treatment until they experience an undesirable side effect, their disease progresses or until they withdraw consent.
The aim of the study is to evaluate the role of lifestyle and environmental factors ( environmental contaminants such as Cd) on the penetrance of BRCA1/2 genes in BRCAm patients with Breast cancer and/or Ovarian cancer and in BRCAm healthy women without cancer diagnosis
The purpose of this phase 1 clinical trials is to determine whether niraparib (a Poly (ADP-ribose) polymerase inhibitor (PARPi)) can be safely combined with irinotecan with manageable toxicity and reasonable efficacy. Emerging evidence suggest that PARPi is an effective therapeutic strategy in a wider subset of solid tumors that may have defective homologous recombination (HR) or DNA repair gene mutations. BReast CAncer gene (BRCA), partner and localizer of BRCA2 (PALB2), and various other DNA repair germline mutations predispose carriers to cancers of the breast, ovaries, pancreas, prostate and melanoma. A number of preclinical studies have demonstrated that PARP inhibitors can work as chemopotentiators. There is significant interest in this combination, and the recommended phase II dose will be used in the upcoming NCI ComboMatch trial.
In BriTROC-2, up to 250 women with a confirmed diagnosis of high-grade serous/high-grade endometrioid or carcinosarcoma will be eligible for full consent (Part 2) and registration to BriTROC-2 and will be followed prospectively until first relapse. Women with presumed newly-diagnosed high-grade serous carcinoma of the ovary, fallopian tube or peritoneum can be approached for consent to Part 1 (screening consent) of BriTROC-2 prior to formal diagnosis. The aim of this study is to acquire tumour material at diagnosis and relapse, whole blood for genomic analysis and plasma for ctDNA. This study will also isolate single cells and establish organoid cultures from ascites/peritoneal washings.
Phase 2 open-label, single-arm clinical trial evaluating the efficacy and safety of neoadjuvant olaparib + LHRH agonist administered for 6 months prior to radical prostatectomy (RP) in men with unfavorable intermediate-risk or high-risk localized prostate cancer. All patients must have confirmed germline or somatic BRCA1/2 gene mutation. Germline and somatic mutation testing will be performed as part of commercially available CLIA assays and will be validated on a uniform platform centrally all patients retrospectively. Eligible patients will receive treatment with olaparib + LHRH agonist. Following 6 months of therapy, patients will undergo RP with mandatory lymph node dissection. The lymph node dissection template will be at the discretion of the treating urologist. RP specimens will undergo pathology blinded independent central review. Following RP, patients will be followed for testosterone recovery and PSA progression.
This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC). Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied