Plymouth

Researchers are evaluating the safety and effects of the study medicine PF-07799933 in people aged 16 and older who have advanced solid tumors with specific BRAF gene alterations. The trial includes participants whose cancers have progressed despite available treatments. This phase 1 open-label study aims to learn about the tolerability, pharmacokinetics, and anti-tumor activity of PF-07799933 given alone and combined with other study medicines. All participants will receive PF-07799933 tablets twice daily. Depending on the tumor type and study part, some participants may also receive binimetinib tablets twice daily, or cetuximab injections weekly or every two weeks in the clinic. Participants with colorectal cancer may also receive mFOLFOX6 chemotherapy, which includes fluorouracil, leucovorin, and oxaliplatin given intravenously. The study involves dose escalation and expansion phases, with treatment lasting about 2 years. Participants will attend regular clinic visits for monitoring during treatment. Researchers will assess dose-limiting toxicities, adverse events, changes in laboratory tests, vital signs, and physical exams from baseline through 28 days after the last dose. Dose interruptions, modifications, and discontinuations due to side effects will be tracked up to 2 years. The overall response rate to treatment will also be measured during this period.

Researchers are evaluating surgical and minimally invasive treatments for lumbar spinal stenosis (LSS) by comparing Medicare patients who received the MILD procedure against those who had interspinous process decompression (IPD). The study focuses on outcomes such as the rate of harms related to the initial procedure and the frequency of additional surgical or minimally invasive interventions within 24 months after treatment. Enrollment includes patients treated from January 1, 2017, onward, with continuation until the sponsor decides to stop. The MILD procedure involves percutaneous image-guided lumbar decompression, performed under fluoroscopy through a dorsal approach to partially remove tissue and bone at the affected spinal level. The control group receives the IPD procedure for LSS. Both groups are monitored for a 24-month period post-index procedure using Medicare claims data to track reoperations and any harms. Participants contribute data through Medicare claims without needing prior enrollment or consent, as the study is exempt from IRB oversight. Researchers collect and analyze information on procedure-related harms and subsequent interventions over two years. This approach allows evaluation of long-term safety and effectiveness outcomes for patients treated with either MILD or IPD.

Researchers are evaluating the effectiveness of BHV-7000 in treating adults with refractory focal onset epilepsy, a condition where seizures originate in specific areas of the brain and have not responded to previous treatments. This Phase 2/3 trial aims to assess the safety, tolerability, and ability of BHV-7000 to reduce seizure frequency in participants who continue to have seizures despite using anti-seizure medications. The study follows classification criteria set by the International League Against Epilepsy and includes participants aged 18 to 75 years. Participants will be randomly assigned to receive either BHV-7000 at doses of 50 mg or 75 mg once daily, or a matching placebo, in a double-blind setup where neither participants nor researchers know which treatment is given. The treatment period focuses on monitoring changes in seizure frequency over 28-day averages from baseline through weeks 8 to 16. The study design includes careful control and comparison to evaluate the investigational drug's impact. During the study, participants will keep accurate seizure diaries to track their seizures. Researchers will measure changes in the average number of seizures over 28-day periods as the primary outcome. Safety and tolerability will also be monitored closely. The study requires participants to be currently treated with one to three anti-seizure medications and to meet specific epilepsy criteria. Overall participation includes screening, treatment, and follow-up to assess the drug's effects and participant safety.

Researchers are investigating multi-cancer detection (MCD) tests as a new way to screen for multiple cancers at once in adults aged 45 to 75 without cancer. This study is a feasibility trial called the Vanguard Study designed to explore how well these MCD tests work as cancer screening tools and to understand how patients and doctors decide on care based on the test results. The study will compare two different MCD tests to a control group, aiming to provide early information on their performance and impact. Participants are randomly assigned to one of three groups: one group will have blood collected for the Shield MCD test, another for the Avantect MCD test, and a control group will have blood collected without MCD testing. Blood samples are collected at enrollment and again after one year. Some sites will share test results with participants, while others will keep results blinded. After the intervention period, participants will be followed passively for up to 10 years. During the study, participants complete baseline and follow-up questionnaires within 60 days, provide blood samples for MCD testing within 90 days, and allow researchers to collect health data from medical records. The study measures enrollment feasibility, follow-up completion, diagnostic resolution of abnormal results, test accuracy, and participant anxiety related to the testing process. Safety and long-term outcomes such as cancer incidence and mortality are also monitored throughout the study period.