You have reached the maximum number of saved studies (100). Patients receive trametinib PO QD. Fisher exact tests and logistic regression models will be used to evaluate the relationships between specific variations and treatment response. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. When these proteins are blocked, the growth of cancer cells may be stopped and the cancer cells will then die. Markers of cell proliferation (Ki67) and apoptosis (p27) will also be assessed. Matthew Benjamin Rettig, Chat with us: LiveHelp The treating physician may advise him stop compassionate used of trametinib or may advise him to lower the dose. To assess the activity of trametinib in metastatic castration resistant prostate cancer (mCRPC) that has progressed on either enzalutamide or abiraterone acetate. Use the checklist in our guide to gather the information you'll Trametinib, a highly specific and potent MEK1/2 inhibi- tor, is approved by the Food and Drug Administration (FDA) for the treatment of BRAF-mutated metastatic mel- anoma. XIV. (Clinical Trial), A Single-Arm, Open-Label, Two-Stage Phase II Study of the MEK 1/2 Inhibitor Trametinib in Men With Progressive Metastatic Castrate Resistant Prostate Cancer, 18 Years and older (Adult, Older Adult), UCLA / Jonsson Comprehensive Cancer Center, Los Angeles, California, United States, 90095. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Summary. Overall survival measured as time from enrollment until death. Clinically significant cardiovascular disease including: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. Those patients with World Health Organization (WHO) grade 1 or 2 glioma were classified as having low-grade glioma (LGG; n = 13) and those with WHO ⦠Statistical bootstrap and Pearsons Correlation will be used to determine the relationship of phenotype to mutations and clinical variables. Investigation of molecular correlates to resistance and sensitivity to trametinib using pre-treatment and at progression metastatic biopsies. XI. Analyses of circulating tumor deoxyribonucleic acid (ctDNA) for genomic aberrations correlated to treatment response. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. XII. Lead Organization Spartalizumab Triplet Does Not Improve PFS in Metastatic Melanoma. Time to initiation of alternative antineoplastic therapy. Safety and tolerability. Une opération chirurgicale pour enlever la vessie; Un traitement général par chimiothérapie; Un traitement par radiothérapie; Les traitements des cancers de vessie métastatiques; Le rétablissement urinaire. Itâs important to counsel the patient about how to manage them using Tylenol to reduce the fever and to reassure the patient that this is not an indication that the treatment is not working or that the cancer is growing or ⦠Treatment continues in the absence of disease progression or unacceptable toxicity. Why Should I Register and Submit Results? Read our, ClinicalTrials.gov Identifier: NCT02881242, Interventional
⦠Talk with your doctor and family members or friends about deciding to join a study. In the Mixed effects logistic regression models to assess changes in markers over time, correlations between markers over time and associations between markers and treatment response (conditional logistic regression) will be used. Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer . GDSC2 GDSC1. Quality of life by Functional Assessment of Cancer Therapy- Prostate (FACT-P). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trametinib ⦠Trametinib may also be stopped completely at his ⦠Will be defined as decline in PSA of 30% or more, any decline of PSA of 50% or more, partial or complete response at 12 weeks, and freedom from radiographic progression at 24 weeks. Dataset. Why Commemorate 50 Years of the National Cancer Act? trametinib - As monotherapy for the first-line and second-line treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, according to specific criteria trametinib - In combination with dabrafenib for the treatment of BRAF V600 mutation-positive, unresectable or metastatic melanoma, according to specific clinical criteria I. XII. Analysis of trametinib target engagement of mitogen-activated extracellular signal-related kinase (MEK1/2) is assessed by presence of p-ERK, the primary phosphorylation target of activated MEK1/2, in pre-treatment and at progression radiographically directed metastatic tumor biopsies by immunohistochemistry evaluation of p-ERK. Quality of life by Functional Assessment of Cancer Therapy- Prostate (FACT-P). I. Durability of prostate specific antigen (PSA) response as measured by the time to PSA progression as defined by Prostate Cancer Working Group 2 guidelines for PSA progression. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Enrichment for patients in the second phase who have tumors exhibiting genomic features associated with a response to trametinib. Analysis of trametinib target engagement of mitogen-activated extracellular signal-related kinase (MEK1/2) is assessed by presence of p-ERK, the primary phosphorylation target of activated MEK1/2, in pre-treatment and at progression radiographically directed metastatic tumor biopsies by immunohistochemistry evaluation of p-ERK. ... [1.5 mg trametinib (continuous)/50 mg afuresertib (Days 1-10 every 28 days)] was evaluated and considered tolerable. Call us:1-800-4-CANCER(1-800-422-6237). Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells. Although the combination has a manageable safety profile, many toxicities associated with the regimen may not be familiar to thoracic specialists or general oncologists. VIII. JNCCN Spotlights. The 1 main adverse effectâ¦with this combination is fever. UCLA / Jonsson Comprehensive Cancer Center, Principal Investigator The majority of study participants, 120 patients, had received prior chemotherapy for mCRC and 14 were treatment-naive. XII. The findings were recently published in the New England Journal of Medicine. This phase II trial studies how well trametinib works in treating patients with castration-resistant prostate cancer that is growing or getting worse and has spread to other parts of the body. Investigation of molecular correlates to resistance and sensitivity to trametinib using pre-treatment and at progression metastatic biopsies. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Product Manufactured in and Exported from the U.S.: PSA response rate [ Time Frame: At 12 weeks ], Response rate assessed by RECIST criteria [ Time Frame: Up to 24 weeks ], Change in markers of cell proliferation (Ki67) and apoptosis (p27), assessed by immunohistochemistry [ Time Frame: Baseline up to 24 weeks ], Change in trametinib target engagement of MEK1/2 defined by the presence of p-ERK, assessed by immunohistochemistry [ Time Frame: Baseline up to 24 weeks ], Durability of PSA response as measured by time to PSA progression as defined by PCWG2 guidelines [ Time Frame: Up to 30 months ], Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 months ], Maximal PSA response [ Time Frame: Up to 30 months ], Molecular correlates defined by gene expression, assessed using ribonucleic acid-sequencing, and mutational events, assessed using DNA exome-seq [ Time Frame: Up to 24 weeks ], Objective radiographic response rate according to RECIST guidelines [ Time Frame: Up to 24 weeks ], Overall survival [ Time Frame: Time from enrollment until death, assessed for up to 30 months ], Quality of life, assessed by FACT-P [ Time Frame: Up to 30 months ], Time to initiation of alternative anti-neoplastic therapy [ Time Frame: Up to 30 months ], Time to radiographic progression [ Time Frame: Up to 24 weeks ], ctDNA genomic aberrations, assessed by exome sequencing [ Time Frame: Up to 24 weeks ], Willing and able to give informed consent, Histologically confirmed prostate cancer (not exclusive of adenocarcinoma), mCRPC that has progressed on at least 1 therapy progression (defined as Prostate Cancer Working Group 2 [PCWG2] or at investigators' discretion) approved for treatment of mCRPC, one of which must include abiraterone acetate and/or enzalutamide, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, Willing to undergo biopsy of a metastatic lesion at the time of progression, Patients must have ongoing therapy to maintain serum testosterone < 50 ng/dL, Absolute neutrophil count > 1,500/uL during screening evaluation, Platelet count > 100,000/uL during screening evaluation, Hemoglobin > 9 g/dL during screening evaluation, Total bilirubin within the reference range during screening evaluation, Alanine aminotransferase (ALT) within the reference range during screening evaluation, Aspartate aminotransferase (AST) within the reference range during screening evaluation, Creatinine < (1.5 mg/dL) during screening evaluation (> 1.5 is allowed if epidermal growth factor receptor [EGFR] > 45 mL/min/1.73 m^2), International normalized ratio (INR) < 1.3 (or < 3 if on warfarin or other anticoagulants) during screening evaluation, Left ventricular ejection fraction (LVEF) >= 45% as measured by echocardiogram during screening evaluation, Electrocardiogram (EKG) without clinically significant abnormality, A history of retinal vein occlusion (RVO) or risks factors for RVO, A history of retinal pigment epithelial detachment (RPED) or risk factors for RPED, Clinically significant abnormality on ophthalmologic examination during screening evaluation, History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months, New York Heart Association (NYHA) class III or IV congestive heart failure, Clinically significant abnormality on EKG, History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes), Patients with intra-cardiac defibrillators or permanent pacemakers, Presence of a comorbid disease or medical condition that would impair the ability of the patient to receive or comply with the study protocol, History of interstitial lung disease or pneumonitis, Use of any medication or herbal products that may have hormonal anti-prostate cancer activity and/or are known to modulate PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment, Prior use of trametinib or other mitogen activated protein kinase (MAPK) inhibitor in any context, Known or suspected brain metastasis or active leptomeningeal disease or spinal cord compression, Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months, inflammatory bowel disease), Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 30 days of enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days of enrollment, Hospitalization within 30 days of enrollment for cancer related events, History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer, Use of an investigational agent within 4 weeks of enrollment, Use of any medications known to affect the serum androgen level, Any condition or reason that, in the opinion of the investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data. This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has spread to other parts of the body. Patients receive trametinib orally (PO) once daily (QD). Time to initiation of alternative antineoplastic therapy. IV. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Conclusions: The results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals. Treatment continues in the absence of disease progression or unacceptable toxicity. need. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Hepatic dysfunction is frequently found in patients with advanced cancer and usually prevents patients from receiving standard treatments or from participating in clinical trials. Eligible, consenting patients were randomly assigned to receive either trametinib daily or one of five standard of care treatments including: paclitaxel, PLD, topotecan, letrozole, or tamoxifen) until disease progression. To assess the activity of trametinib in metastatic castration resistant prostate cancer (mCRPC) that has progressed on either enzalutamide or abiraterone acetate. study started January 2018. estimated completion January 2023. Complementary & Alternative Medicine (CAM), Coping with Your Feelings During Advanced Cancer, Emotional Support for Young People with Cancer, Young People Facing End-of-Life Care Decisions, Late Effects of Childhood Cancer Treatment, Tech Transfer & Small Business Partnerships, Frederick National Laboratory for Cancer Research, Milestones in Cancer Research and Discovery, Step 1: Application Development & Submission, National Cancer Act 50th Anniversary Commemoration. Patients may also need dose adjustments or absorb drugs differently. Thirty-seven patients with glioma were enrolled and included in the primary analysis. a study on Prostate Cancer. Listing a study does not mean it has been evaluated by the U.S. Federal Government. II. Compound: Trametinib Drug Target: MEK1, MEK2 Drug Target pathway: ERK MAPK signaling . Treatment continues in the absence of disease progression or unacceptable toxicity. Information provided by (Responsible Party): This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has spread to other parts of the body. Trametinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 kinases, which are part of the RAS-RAF-MEK-ERK cell signalling pathway. III. Jefferson University and Hospitals, Inc., G-301 Bodine Cancer Center, 111 South 11th Street Philadelphia, PA 19107. Trametinib inhibits growth of BRAF-mutated cells by blocking the downstream cell signaling by MEK1 and MEK2. Discovery of one or a set of possible discriminative networks that are associated with a response to trametinib. VII. * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
Patients receive trametinib orally (PO) once daily (QD). Chemotherapy regimens, monoclonal antibodies, and targeted therapies such as tyrosine kinase ⦠Enrichment for patients in the second phase who have tumors exhibiting genomic features associated with a response to trametinib. NRG-GOG 0281 assessed whether trametinib, as a potential novel therapeutic, could improve PFS outcomes for women diagnosed with LGSOC. III. The combination of dabrafenib plus trametinib has demonstrated substantial clinical activity in patients with BRAF V600Eâmutant nonâsmall cell lung cancer, leading to U.S. Food and Drug Administration approval. Vivek Subbiah, MD, discussed the positive findings from the phase 2 ROAR clinical trial, which evaluated the targeted therapy combination of dabrafenib and trametinib as treatment of patients with cholangiocarcinoma harboring a BRAF V600E mutation. It is for people who have non small cell lung cancer (NSCLC) that has spread to another part of the body (advanced non small cell lung cancer).. Doctors can treat advanced NSCLC with chemotherapy.This can work for a while but sometimes the cancer begins to grow again. XIV. Please remove one or more studies before adding more. VI. Trametinib may stop the growth of tumor cells by blocking proteins needed for cell growth. ROAR was a nonrandomized, open-label basket study of dabrafenib and trametinib in patients with BRAF V600E mutationâpositive rare cancers. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02881242. RESULTS: A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The dual inhibition of BRAF and MEK was tested in patients with metastatic BRAFV600E colon cancers but ⦠Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. * Patients with intra-cardiac defibrillators or permanent pacemakers, Presence of a comorbid disease or medical condition that would impair the ability of the patient to receive or comply with the study protocol, History of interstitial lung disease or pneumonitis, Use of any medication or herbal products that may have hormonal anti-prostate cancer activity and/or are known to modulate PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment, Prior use of trametinib or other MAPK inhibitor in any context, Known or suspected brain metastasis or active leptomeningeal disease or spinal cord compression, Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months, inflammatory bowel disease), Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 30 days of enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days of enrollment, Hospitalization within 30 days of enrollment for cancer related events, History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer, Use of an investigational agent within 4 weeks of enrollment, Use of any medications known to affect the serum androgen level, Any condition or reason that, in the opinion of the investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data. * LVEF < 45% measured by echocardiogram
VI. IV. After completion of study treatment, patients are followed up at 2 and 4 weeks, and then every 4 weeks thereafter. The goal of this study is learn if the combination of azacitidine, venetoclax, and trametinib can help to ⦠* New York Heart Association (NYHA) class III or IV congestive heart failure
Dabrafenib plus trametinib as a first-line treatment demonstrated long-term survival benefit for approximately one-third of patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, a 5-year pooled analysis of two phase III trials revealed.
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