View clinical trials related to P53 Mutation.
Filter by:To evaluate the safety and effectiveness of Sodium Stibogluconate in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with p53 mutation from a defined list. The list includes 65 p53 mutations that were experimentally confirmed to be pharmacologically restored with tumor-suppressive function by antimonials.
This is an umbrella, two-arm, multi-stage, phase II trial. The purpose of the trial in the early stage cohort is to determine if EBRT improves disease free survival (defined as the time from random assignment to disease recurrence or death from any cause) compared to vaginal brachytherapy after chemotherapy in women with serous or p53 aberrant endometrial cancer. The purpose of the trial in the advanced stage cohort is to determine if the maintenance with experimental treatment increases progression free survival, defined as the time from random assignment to disease progression or death from any cause.
TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Here the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk AML/MDS patients. About 200 AML/MDS patients will be sequenced for TP53 sequence before recruitment. The investigators estimated about 5 patients, based on the reported p53 mutation frequency in AML/MDS, will be p53-mutated. In the trial, the investigators will selectively recruit the mp53 AML/MDS patients that are predicted to respond to DAC+ATO regimen with highest chance (based on the relevant basic studies). The investigators designate mutant p53-based clinical trials as 'PANDA (P53 AND Arsenic)-Trials'.
Part 1 is the dose escalation of APG-115 in combination with label dose of pembrolizumab. Part 2 is phase II design of APG-115 at recommended phase 2 dose (RP2D) in combination with pembrolizumab.
This is a prospective,uncontrolled and multi-institution trial.The aim is to identify if using decitabine,cytarabine and ATO as the therapy of acute myeloid leukemia(AML) with p53 mutations has better relapse free survival and complete response than using decitabine and cytarabine. TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Particularly, p53 mutation is associated with extremely poor prognosis in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients. Decitabine (DAC) is a FDA approved drug for MDS treatment. In two independent clinical trials reported recently, DNA demethylating drug DAC treatment yielded a surprisingly high rate of complete remission (CR) in mp53-harboring AML/MDS patients (Welch, NEJM, 2016; Chang, BJH, 2017). Notably, all of the mp53-expressing patients in the two clinical studies relapsed quickly. Arsenic trioxide (ATO) is a FDA approved drug for M3-AML treatment. Despite of the observed efficacy in treating non-APL patients, ATO is not yet approved for non-APL cancer treatment. ATO plays key role in regulating both wild-type p53 (wtp53) and mp53. Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished). Our unpublished data also suggests a key role of ATO in regulating mp53 (Lu, The 17th International p53 Workshop, 2017). ATO is widely reported to be able to degrade and thus inhibit mp53's oncogenic function (Hamadeh, BBRC, 1999)(Liu, Blood, 2003). ATO suppressed cancer cell growth by targeting mp53 for degradation by Pirh2 degradation pathway (Yang, JBC, 2011; Yan, PLOS one, 2014); Here we explore the potential of combination of DAC and ATO in improving the mp53-harboring AML/MDS patients' relapse free survival (RFS) and the ability to thoroughly eliminate mp53 subclone. Basic researches aiming to explore the mechanisms how mp53 cells responds to DAC and/or ATO treatment and how mp53 cells develop resistance to DAC and/or ATO will be coupled. We designate trials aiming for a better treatment regimen for mp53 patients as 'PANDA-Trials'.
This is a prospective,controlled and multi-institution trial.The aim is to identify if using decitabine and Arsenic Trioxide(ATO) as the therapy of Myelodysplastic Syndrome(MDS) has better relapse free survival and complete response than using decitabine alone. TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Particularly, p53 mutation is associated with extremely poor prognosis in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients. Decitabine (DAC) is a FDA approved drug for MDS treatment. In two independent clinical trials reported recently, DNA demethylating drug DAC treatment yielded a surprisingly high rate of complete remission (CR) in mp53-harboring AML/MDS patients (Welch, NEJM, 2016; Chang, BJH, 2017). Notably, all of the mp53-expressing patients in the two clinical studies relapsed quickly. Arsenic trioxide (ATO) is a FDA approved drug for M3-AML treatment. Despite of the observed efficacy in treating non-APL patients, ATO is not yet approved for non-APL cancer treatment. ATO plays key role in regulating both wild-type p53 (wtp53) and mp53. Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished). Our unpublished data also suggests a key role of ATO in regulating mp53 (Lu, The 17th International p53 Workshop, 2017). ATO is widely reported to be able to degrade and thus inhibit mp53's oncogenic function (Hamadeh, BBRC, 1999)(Liu, Blood, 2003). ATO suppressed cancer cell growth by targeting mp53 for degradation by Pirh2 degradation pathway (Yang, JBC, 2011; Yan, PLOS one, 2014); Here we explore the potential of combination of DAC and ATO in improving the mp53-harboring AML/MDS patients' relapse free survival (RFS) and the ability to thoroughly eliminate mp53 subclone. Basic researches aiming to explore the mechanisms how mp53 cells responds to DAC and/or ATO treatment and how mp53 cells develop resistance to DAC and/or ATO will be coupled. We designate trials aiming for a better treatment regimen for mp53 patients as 'PANDA-Trials'.