Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: NucMito Pharmaceuticals Co. Ltd.
Must not be taking: CYP1A2, CYP3A4, Torsade drugs
Disqualifiers: End organ failure, Other malignancy, ECG abnormalities, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study is to assess the MTD and RP2D of NM6603 in adult patients with advanced solid tumors.
Will I have to stop taking my current medications?
The trial does not specify if you must stop all current medications, but you cannot take certain drugs that affect heart rhythm or specific liver enzymes. If you're on these, you may need to stop them for a period before joining the trial.
What data supports the effectiveness of the drug NM6603 for cancer treatment?
Research on similar treatments shows that targeting the p53 pathway, which is often mutated in cancers, can be effective. For example, the small-molecule NSC59984 restores normal p53 function and activates p73, leading to cancer cell death with minimal harm to normal cells.
12345Eligibility Criteria
Adults with advanced solid tumors that have progressed despite previous treatments can join this trial. They must be over 18, able to swallow pills, and have a life expectancy of at least 12 weeks. Key health requirements include good kidney function, no serious urine test issues, an ECOG performance status of 0-2 (which measures how cancer affects daily living abilities), and adequate bone marrow reserve and liver function. Women who can get pregnant and men must agree to use birth control during the study.Inclusion Criteria
My cancer diagnosis was confirmed through tissue or cell testing.
I am 18 years old or older.
I can take care of myself and perform daily activities.
My kidney function is good, with a filtration rate of 60 mL/min or more.
My blood tests show enough white blood cells, platelets, and hemoglobin.
My liver is functioning within the required limits.
My cancer has grown or spread, confirmed by recent scans.
My advanced cancer does not respond to standard treatments.
Exclusion Criteria
I am mentally and physically capable of participating in a clinical trial.
I have been on steroids equivalent to 7.5 mg of prednisone daily for over 4 weeks in the last 3 months.
I have a history of long QT syndrome or my heart's electrical cycle is longer than normal.
I have no other cancers except for certain skin cancers or cervical cancer in situ in the last 3 years.
I need medication that could cause heart rhythm problems.
Participant Groups
The trial is testing NM6603's maximum tolerated dose (MTD) and recommended phase two dose (RP2D) in patients with advanced solid tumors. The goal is to find out the highest dose patients can take without severe side effects and the optimal dose for further studies.
1Treatment groups
Experimental Treatment
Group I: Dose EscalationExperimental Treatment1 Intervention
NM6603, administered orally every day in 28-day cycles
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Cleveland Clinic Taussig Cancer CenterCleveland, OH
Karmanos Cancer InstituteDetroit, MI
Tennessee Oncology, PLLCNashville, TN
MD Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
NucMito Pharmaceuticals Co. Ltd.Lead Sponsor
References
Manipulation of the tumor suppressor p53 for potentiating cancer therapy. [2022]The tumor suppressor p53 is a linchpin in the regulation of appropriate cellular responses to various stress conditions. Inactivation of the functions of this critical participant can have diabolical consequences, in particular the development of malignant diseases. Elicitation of appropriate p53 functions is an attractive strategy for combating cancer. Triggering p53 responses, reconstituting p53 activities through gene therapy, coercing mutant p53 to perform normal functions, manipulating p53 regulators, and activating p53 effectors are all approaches that are currently being developed. Here, we will overview 'p53-based' strategies for fighting cancer, both those under clinical trial and recent innovative concepts.
The p53-Mdm2 pathway: targets for the development of new anticancer therapeutics. [2019]The tumour suppressor p53 is at the centre of a network of regulatory pathways that guard over the continued integrity of the living cell and its progeny after exposure to different forms of stress, particularly those capable of inducing DNA damage. Tumour cells very frequently circumvent this control by disabling the function of p53, or other proteins in the p53 network, through mutation. Here we review the different therapeutic strategies that have been adopted to exploit common neoplastic aberrations in the p53 pathways. We emphasise in particular those approaches where modulation with pharmaceutical agents has already shown some promise, including pharmacological rescue of mutant p53, modulation of the protein-protein interaction between p53 and one of its negative regulators, Mdm2, as well as interference with downstream targets.
P63 and P73 Activation in Cancers with p53 Mutation. [2022]The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.
Phase I trial using patupilone (epothilone B) and concurrent radiotherapy for central nervous system malignancies. [2012]Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies.
Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53. [2022]The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to tumorigenesis, tumor progression, and chemo- or radiotherapy resistance. Thus, targeting mutant p53 to restore a wild-type p53 signaling pathway provides an attractive strategy for cancer therapy. We demonstrate that small-molecule NSC59984 not only restores wild-type p53 signaling, but also depletes mutant p53 GOF. NSC59984 induces mutant p53 protein degradation via MDM2 and the ubiquitin-proteasome pathway. NSC59984 restores wild-type p53 signaling via p73 activation, specifically in mutant p53-expressing colorectal cancer cells. At therapeutic doses, NSC59984 induces p73-dependent cell death in cancer cells with minimal genotoxicity and without evident toxicity toward normal cells. NSC59984 synergizes with CPT11 to induce cell death in mutant p53-expressing colorectal cancer cells and inhibits mutant p53-associated colon tumor xenograft growth in a p73-dependent manner in vivo. We hypothesize that specific targeting of mutant p53 may be essential for anticancer strategies that involve the stimulation of p73 in order to efficiently restore tumor suppression. Taken together, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by targeting GOF-mutant p53 and stimulates p73 to restore the p53 pathway signaling.