P53 Mutation

Researchers are evaluating AMXI-5001, an oral drug that blocks PARP and microtubule polymerization, in adults with advanced cancers that have not responded to other treatments. This Phase I/II trial aims first to find the best dose and then to study the drug's safety and effects in more detail. The study includes participants with several types of advanced cancers, including breast, ovarian, prostate, pancreatic, and other malignant tumors. The trial has two parts: Phase I involves dose escalation, where up to 70 participants receive AMXI-5001 orally twice a day with food on a weekly continuous 7-day schedule, with each treatment cycle lasting 28 days. After determining the recommended dose, Phase II will enroll up to 52 participants to further assess safety, drug levels in the blood, and anti-tumor activity using the chosen dose. All participants receive the study drug as monotherapy. Participants will be monitored for safety, drug concentration in plasma, and tumor response using standard imaging and laboratory tests over approximately 24 months. The primary goals include finding the maximum tolerated dose and recommended dose for Phase II, as well as characterizing the safety profile. Participants must consent and meet eligibility criteria related to their cancer status and overall health. The trial will continue until about October 2026.

Researchers are evaluating if the study drugs abemaciclib and letrozole are effective and safe for people with advanced or recurrent estrogen receptor-positive (ER+) endometrial cancer that is mismatch repair proficient and has tumor protein p53 (TP53) wild-type. This phase 2, single arm trial focuses on maintenance treatment following chemotherapy with or without anti-PD-(L)1 blockade. The FDA has not approved these drugs for endometrial cancer but has approved them for other uses. Participants will receive abemaciclib tablets twice daily and letrozole tablets once daily in 21-day cycles. Treatment will continue for up to 2 years. Scans such as X-rays, CT, MRI, or PET will be done every 9 weeks for the first 9 months, then annually. After treatment ends, participants will have assessments and continue follow-up for up to 3 years. The study is supported by Eli Lilly, which provides funding and the abemaciclib drug. During the study, participants will undergo screening and regular evaluations including scans, blood tests, and electrocardiograms (EKGs). Researchers will monitor progression-free survival over 2 years as the primary outcome. Secondary outcomes include adverse event rates, overall survival up to 5 years, and objective response rate. Participants must have good performance status and normal organ function to join and will be followed closely throughout treatment and follow-up periods.

Researchers are evaluating the safety and effectiveness of arsenic trioxide combined with chemotherapy for treating pediatric cancer patients who have p53 mutations. These mutations are linked to Li-Fraumeni syndrome, a hereditary condition that greatly increases the risk of developing multiple cancers at a young age. Current treatments for this condition are limited and often involve DNA-damaging therapies that can lead to additional tumors. This study aims to explore a treatment that targets mutant p53 without causing DNA damage, which could offer new options for affected children. Participants will first receive their standard first-line chemotherapy for their specific cancer type. If the cancer does not respond or remains stable, arsenic trioxide will be added to their existing chemotherapy regimen starting on the third day of each treatment cycle. The arsenic trioxide is given intravenously at a dose based on body weight, over six hours daily for ten days during each cycle. This approach will be tested in a single-arm, multi-center trial that also includes laboratory experiments to confirm arsenic trioxide’s ability to restore p53 function in the patient’s specific mutation. During the study, participants will be closely monitored with regular assessments of their cancer’s response to treatment, including measurements of tumor size four weeks after starting arsenic trioxide combined therapy. Researchers will also track progression-free survival, overall survival, and any adverse events for up to three years. Guardians will provide informed consent, and patients must have measurable tumors and confirmed p53 mutations that respond to arsenic trioxide in lab tests. This careful monitoring aims to ensure safety and gather important data on the treatment’s impact over time.

Researchers are studying the effects of Hyperbaric Oxygen Therapy (HBOT) in patients undergoing radiotherapy for cancer or other neoplastic diseases. HBOT involves breathing oxygen at higher than normal pressures, which increases oxygen levels in tissues and promotes wound healing. However, this increased oxygen can produce reactive oxygen species (ROS) that may cause DNA damage and raise long-term cancer risks. The study aims to understand how repeated HBOT sessions impact DNA damage, especially in patients with impaired DNA repair due to cancer or related conditions. Participants will undergo HBOT sessions as part of their treatment for radiation-related complications or other indications. The study involves blood tests taken before and after the first HBOT session and immediately after the last session to measure DNA damage and ROS production. Researchers will track these changes throughout the course of treatment to explore correlations between HBOT, DNA damage, and wound healing after radiotherapy. During the study, participants will provide blood samples at key time points to assess DNA damage and ROS levels. The main outcome is the correlation between HBOT sessions and DNA damage at baseline, after the first session, and after the last session. Additional measures include monitoring ROS formation and examining links between DNA damage and healing of radiation-induced wounds. The study is conducted under medical supervision, ensuring participant safety and thorough evaluation over the treatment period.

Researchers are evaluating the effectiveness and side effects of combining Azacitidine with R-CHOP chemotherapy in treating patients with newly diagnosed TP53-mutated Diffuse Large B-cell Lymphoma (DLBCL). This Phase 2, open-label study focuses on important outcomes like complete remission, overall survival, and progression-free survival. Participants will receive a specified dose of Azacitidine subcutaneously from day 1 to day 5, along with R-CHOP components including Rituximab, Cyclophosphamide, Epirubicin or Liposomal Adriamycin, Vincristine, and Prednisone administered on scheduled days. The study involves a single treatment arm using this combination, monitored over a period of up to 36 months. During the study, participants will undergo regular assessments to measure response rates such as complete and partial remission, overall response, and progression-free survival. Safety and side effects will be closely monitored throughout. The study aims to follow participants for up to three years to understand long-term outcomes and treatment effects.

Researchers are evaluating the effectiveness of bipolar androgen therapy (BAT) combined with carboplatin in men who have metastatic castrate-resistant prostate cancer (mCRPC). This condition progresses despite low testosterone levels, and while androgen deprivation therapy (ADT) is standard, resistance develops over time. The study explores whether cycling testosterone levels can improve responses, particularly in men with DNA repair defects. Participants receive high dose testosterone enanthate injections of 500mg intramuscularly every 4 weeks alongside continuous LHRH therapy or after surgical removal of the testes, plus carboplatin chemotherapy dosed at AUC 5. This combination is being studied in a phase 2 trial to assess how well it works and its safety. During the study, men's prostate-specific antigen (PSA) levels will be monitored over one year to evaluate treatment response. Imaging and safety assessments will also occur to track disease progression and side effects. Participants must comply with scheduled visits, lab tests, and biopsies as part of the study, which is sponsored by St Vincent's Hospital in Sydney.

Researchers are evaluating the safety and effectiveness of combining camrelizumab with fluzoparib as maintenance therapy in patients with recurrent or metastatic TP-53 mutated endometrial cancer. This open-label Phase II randomized controlled trial involves 117 participants and aims to explore how common homologous recombination deficiency is in Chinese patients with this mutation and its impact on treatment outcomes. The study addresses the need to optimize treatment strategies for this specific patient group due to mixed results from previous trials involving chemotherapy and immunotherapy combinations. Participants receive an initial treatment period including intravenous injections of paclitaxel (albumin-bound) at 260 mg/m2, carboplatin at an AUC of 5, and camrelizumab at 200 mg every three weeks for six cycles. Radiation therapy may be given based on the investigator’s decision. Following this, patients enter a maintenance phase where camrelizumab is administered intravenously every three weeks, with or without oral fluzoparib capsules taken twice daily, continuing until disease progression, intolerable side effects, death, or up to two years. During the study, participants undergo regular assessments to monitor their health and treatment response, including evaluation of progression-free survival at 12 months, duration of response, and overall survival up to 24 months. The trial requires participants to comply with clinic visits and follow-up schedules. Researchers also collect tumor tissue samples to test for homologous recombination deficiency. Safety is closely monitored throughout the treatment and maintenance phases to ensure participant well-being.

Researchers are studying Canadian cancer patients who have rare genetic changes in their tumors, such as alterations in genes like ALK, EGFR, ROS1, BRAF, and KRAS G12C. These rare molecular alterations can affect how the cancer responds to certain targeted drugs called tyrosine kinase inhibitors (TKIs). The study aims to better understand the natural history of these cancers and compare treatment outcomes, including side effects and patient-reported experiences, across different therapies. The study observes cancer patients who have received or are currently receiving TKIs or other targeted therapies. It includes three groups: living patients with confirmed rare molecular alterations, deceased patients with such alterations, and a comparator group of cancer patients without these rare changes. Patient-reported outcomes are collected through surveys at baseline and every three months, especially when treatments change. Participants provide molecular testing reports and complete quality of life questionnaires regularly for up to 10 years. Researchers track progression-free survival or overall survival, the development of brain metastases, and economic impacts related to treatment. The study collects data from medical records and patient surveys to understand treatment patterns, effectiveness, and quality of life in the real-world Canadian context.

Researchers are studying individuals who have known or suspected metabolic, inflammatory, or genetic conditions that may increase their risk for heart and blood vessel diseases. This includes both affected individuals and unaffected relatives or healthy volunteers. The study aims to understand rare and uncommon diseases related to cardiovascular dysfunction, identify genetic factors, and discover new disease mechanisms to expand knowledge and support future research and treatment development. Participants may undergo various tests, depending on their condition. These tests include photography of the face and body, body measurements, X-rays, metabolic stress testing, echocardiography, MRI scans including cardiovascular imaging, CT angiograms, PET imaging, six-minute walk tests, and vascular ultrasounds. Blood, tissue, and other samples may be collected during the study or surgical procedures. The study includes children over 1 year old with diseases or relatives of affected individuals, healthy adult volunteers 18 and older, and adults with known or suspected cardiovascular-related pathologies. During the study, participants will provide samples and undergo evaluations tailored to their condition. Researchers will assess heart, blood vessel, and lung function through various imaging and functional tests. They will monitor disease diagnosis, potential genetic counseling, and understanding of disease processes. The study may include follow-up visits or additional protocols to further study specific diseases or pursue innovative treatments. Participation can last as long as needed to complete these evaluations and follow-ups.

This research aims to collect detailed information on the history and real-world treatment of patients diagnosed with chronic lymphocytic leukemia (CLL) across multiple centers in Turkey. The study seeks to better understand how CLL is managed in both community and academic healthcare settings and to evaluate the effectiveness of first, second, and later treatment strategies used for this condition. As an observational study, it does not involve experimental treatments or interventions but instead gathers data from patients diagnosed with CLL. The study follows patients over time to observe the distribution of first-line therapy protocols within 36 months. This approach allows researchers to see how treatments are applied in everyday clinical practice and their outcomes. Participants will be involved through regular data collection regarding their diagnosis and treatment history. Researchers will review medical records and treatment patterns to assess therapy use and outcomes. The primary outcome measure focuses on the types of first-line therapy given over a three-year period. The study spans several years, starting in 2017 and continuing through at least August 2026.