View clinical trials related to PALB2 Gene Mutation.
Filter by:This is an open label, phase II trial in subjects with treatment naïve, metastatic hormone sensitive prostate cancer (mHSPC) with deleterious HRR alteration(s). These include pathologic alterations in BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. A total of 64 people will be enrolled to the study.
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).
Circulating levels of Sex Hormone Binding Globulin (SHBG) are significantly associated with a decreased risk of breast cancer. The main aim of this clinical trial is to verify whether Low Dose Tamoxifen (LDT) increases circulating levels of SHBG more than lifestyle intervention (LI) with or without intermittent caloric restriction (ICR) after 6 months in women at increased risk of breast cancer (i.e., healthy participants carriers of a germline pathogenic/likely pathogenetic variant in at least one of the following genes: BRCA1, BRCA2, PALB2, ATM, CHEK2, CDH1, RAD51C or RAD51D, or with > 5% breast cancer risk at 10 years, using the Tyrer Cuzick or the Breast Cancer Surveillance Consortium Risk models or with a recently resected intraepithelial neoplasia of the breast (IEN). The secondary aims are: - to verify whether ICR significantly modulates primary and secondary endpoints such as Homeostasis Model Assessment (HOMA) index, immune and inflammatory markers, lipid profile, Adiponectin/Leptin (A/L) ratio, quality of life (QoL), Body mass index (BMI), fat body composition, safety and toxicity; - to verify whether LDT significantly modulates secondary endpoints, such as HOMA-index, immune and inflammatory markers, lipid profile, A/L ratio, QoL, BMI, fat body composition, safety and toxicity; - to investigate differences in microbiome composition by arms and the effect of changes in microbiome on QoL taking into account circulating biomarkers, cytokines, immune modulators, and inflammatory proteins in serum; - to investigate MD (Mammographic Breast Density) changes by LDT vs. LI, with or without ICR. This aim will be performed in a subgroup of participants (not all the participants will undergo mammography due to younger age).
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.
The long-term goal of our PIC is to develop effective strategies that can be applied clinically at the point-of-care to prevent, intercept, or detect PDAC at an early stage, thereby reducing PDAC burden and saving lives.
The purpose of this study is to evaluate a cascade genetic testing intervention. Cascade testing is the process of offering genetic testing to people who are at risk of having inherited a possibly harmful gene change that has been found in their family. This process is repeated as more people within the family are found to have the gene change. The study will look at how often genetic testing occurs when healthcare providers have permission to reach out to family members to recommend genetic testing and to help those who are interested get tested. The study will look at whether this cascade testing intervention is practical and effective. The study would like to see how this approach of healthcare providers reaching out directly to family members compares with the usual approach of patients telling their family members about the recommendation to get genetic testing.
The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic cancer in patients who have a deleterious or suspected deleterious BRCA1, BRCA2, or PALB2 genetic alteration. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, low-dose I.V. ethanol, vitamin B12b, and vitamin C in association with autologous hematopoietic stem cell infusion. A dose-escalation schedule will be employed for vitamin C.
This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
This research study is for patients with metastatic breast cancer. - Metastatic means that the cancer has spread beyond the breast. In addition, through genetic testing of the blood or tumor, an altered gene has been found that suggests the tumor may not be able to repair its genetic material (DNA) when it becomes damaged. - This aspect of the cancer may cause it to be more sensitive - that is, more effectively killed by certain types of drugs such as the study agent being evaluated in this trial, Olaparib. - Olaparib is a type of drug known as a PARP inhibitor. Some types of breast cancer and ovarian cancer share some basic features that make them sensitive to similar treatments. Information from those other research studies suggests that this drug may help to treat metastatic breast cancer. - This study will evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in one of the other genes that function with BRCA1 and BRCA2 to repair damaged DNA .This mutation may have been inherited from a parent, or may have developed only in the tumor. - This study will also evaluate whether olaparib is effective in breast cancer patients whose tumor has a mutation in BRCA1 or BRCA2 that was acquired by the tumor, but not inherited.