Burlingame

Researchers are evaluating the safety and effectiveness of Vagus Nerve Stimulation (VNS) Therapy as an additional treatment compared to no stimulation in people with treatment-resistant depression. This prospective, multi-center, randomized, controlled, blinded trial focuses on reducing depressive symptoms over 12 months using multiple depression rating scales. The study follows guidelines from the Centers for Medicare and Medicaid Services regarding evidence development for this treatment. Participants receive implantation of the VNS device, which delivers stimulation to the vagal nerve. After a minimum two-week period post-implantation, participants are randomly assigned to either active VNS treatment or no stimulation control, with outcomes observed for 12 months. Following this randomized phase, all participants enter an open-label extension where those in the control group receive active stimulation. Additional subjects may join this open-label study for up to five years to further assess long-term effects. Throughout the study, participants undergo regular assessments including the Montgomery Åsberg Depression Rating Scale (MADRS), WHO Disability Assessment Schedule, Health Outcome Scale, Clinical Global Impressions Scale, and Suicidality Tracking Scale. Researchers monitor response rates, remission times, duration of effects, and adverse events from implantation through 12 months. This comprehensive evaluation includes safety monitoring and functional outcome measures to understand the impact of VNS therapy on depression and related disabilities.

Researchers are evaluating the safety and effectiveness of the BWI OMNYPULSE123 pulsed field ablation (PFA) system, including the OMNYPULSE123 catheter and TRUPULSE123 generator, for treating people with symptomatic paroxysmal atrial fibrillation (PAF). PAF is an irregular heart rhythm that affects blood flow, and this study aims to demonstrate the safety and 12-month effectiveness of this treatment for pulmonary vein isolation (PVI). Participants will receive treatment using the OMNYPULSE123 catheter with the TRUPULSE123 generator for pulsed field ablation. The study focuses on using this device to isolate pulmonary veins as a method to manage paroxysmal atrial fibrillation. The procedures and device usage are designed to be evaluated over a 12-month period following the treatment. During the study, participants will be monitored for adverse events within 7 days after the procedure and will be assessed for freedom from atrial tachyarrhythmia episodes (including atrial fibrillation, atrial tachycardia, or atrial flutter) from day 91 to day 365 post-procedure. Researchers will conduct follow-up visits and tests to evaluate safety and treatment outcomes over the full year after treatment.

Researchers are evaluating the safety and effectiveness of the Trilogy Transcatheter Heart Valve (THV) System compared with surgical aortic valve replacement (SAVR) in patients with significant native aortic regurgitation (AR). The study aims to show that the Trilogy THV system is not worse than SAVR for treating this condition. This trial includes adults who have clinically significant AR needing valve replacement according to established heart guidelines. Participants are assigned to receive either the Trilogy THV device via transcatheter aortic valve replacement (TAVR) or undergo SAVR using commercially approved surgical prosthetic valves. The study monitors treatment outcomes over 12 months, focusing on all-cause mortality, all strokes, and unplanned cardiac rehospitalizations. Both procedures are delivered according to standard clinical practice for valve replacement. During the study, participants will attend follow-up visits for evaluations and monitoring. Researchers will assess outcomes such as survival, stroke occurrence, and heart-related hospital readmissions within one year. The study requires participants to agree to return for all follow-up visits to track these outcomes and ensure safety throughout the trial period.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer after surgery by using the presence or absence of circulating tumor DNA (ctDNA) in the blood. This approach aims to identify microscopic residual tumor cells and may provide better risk prediction for cancer recurrence compared to traditional methods. The trial focuses on patients with Stage IIB, IIC, or III colon cancer who have undergone complete tumor removal. Participants will have their tumor tissue and blood tested centrally using the Signatera assay to determine ctDNA status. Patients without detectable ctDNA may avoid chemotherapy, while those with detectable ctDNA are considered at higher risk and will be randomly assigned to receive different chemotherapy regimens, including mFOLFOX6, CAPOX, or mFOLFIRINOX, given intravenously or orally over periods ranging from 3 to 6 months. The study includes initial screening, treatment, and possible second randomization for patients whose ctDNA status changes during monitoring. During the study, participants will undergo various assessments including blood tests, imaging scans, and performance evaluations to monitor their health and response to therapy. Researchers will track the time to ctDNA positivity and disease-free survival for up to 3 and 5 years, respectively. Safety and treatment effects will be closely observed throughout the study duration, ensuring thorough follow-up and monitoring for all participants.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating a screening and multi-sub-study randomized phase II/III trial called Lung-MAP, designed for patients with previously treated non-small cell lung cancer. The trial aims to establish a genomic screening method to assign patients to biomarker-driven or non-matched sub-studies. Depending on the cancer biomarker type, participants may receive new targeted cancer therapies or combinations compared to standard care, with the goal of approving new treatments. An optional ancillary study explores patient and physician attitudes about returning genetic findings related to germline mutations. The study involves testing patient specimens to determine eligibility for various sub-studies under the Lung-MAP protocol. Patients undergo screening to analyze tumor tissue and blood samples for biomarkers including PD-L1 and c-MET. Those requiring a fresh biopsy also submit blood for circulating tumor DNA testing. Sub-study assignment depends on the molecular profile results. This screening process includes both patients progressing after prior therapy and those pre-screened before progression on current treatment. Participants provide informed consent and tumor tissue that meets quality standards for testing. Researchers collect clinical data including smoking history and performance status. Outcomes focus on screening success, such as adequate tissue submission and matching to biomarker-driven sub-studies, tracked for up to three years. The study also monitors patient and physician knowledge and preferences regarding genomic findings. Participation duration varies based on screening and sub-study assignment.

Researchers are evaluating two chemotherapy treatments, mFOLFIRINOX and mFOLFOX, with or without the immunotherapy drug nivolumab, for advanced, unresectable, or metastatic HER2 negative adenocarcinoma of the esophagus, gastroesophageal junction, and stomach. This phase III trial aims to determine whether adding irinotecan to the usual FOLFOX regimen improves overall survival and other outcomes such as progression-free survival, response rates, and treatment tolerability. The study also explores biomarkers like PD-L1 combined positive score and cell free DNA to understand treatment effects better. Participants are randomly assigned to one of two treatment groups. One group receives fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) with nivolumab as needed, while the other group receives fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) with nivolumab as needed. All drugs are given intravenously. Throughout the trial, patients undergo MRI and CT scans and may provide blood samples for additional testing. During the study, participants are closely monitored for overall survival for up to two years after randomization. Researchers assess safety, side effects, and patient-reported outcomes to evaluate treatment tolerability. The trial also tracks progression of disease and response to therapy using imaging and other clinical evaluations. Participation includes regular imaging, blood collection, and completing questionnaires to help understand the impact of these treatments.

This research aims to find the first effective treatment for acute spontaneous intracerebral hemorrhage (ICH) by studying recombinant Factor VIIa (rFVIIa) given shortly after stroke onset. The trial focuses on patients treated within a critical early time window, either within 120 minutes with a positive spot sign on CT angiography or within 90 minutes regardless of spot sign. The goal is to see if rFVIIa improves functional outcomes at 90 days and reduces ongoing brain bleeding compared to standard care. Participants will be randomly assigned, without knowing which treatment they receive, to either rFVIIa at a dose of 80 micrograms per kilogram (up to 10 mg) or a matching placebo. All participants will also receive the best standard therapy according to guidelines, including blood pressure management targeting a systolic pressure of 140 mm Hg. The study includes a baseline and 24-hour CT scan to measure bleeding and swelling, with follow-up assessments at 30, 90, and 180 days. The trial involves about 100 hospitals and mobile stroke units across several countries, aiming to treat patients quickly after stroke onset. Throughout the study, participants will undergo clinical assessments including the Modified Rankin Scale to evaluate disability at 90 days, which is the main outcome measure. Imaging scans will be analyzed centrally to track hemorrhage size and brain swelling. Safety and recovery will be monitored remotely at multiple time points. The total planned enrollment is up to 350 participants over about three and a half years, with advanced consent procedures to enable rapid treatment delivery in emergency settings.

Researchers are evaluating a phase III trial comparing shorter chemo-immunotherapy without anthracycline drugs to the usual chemo-immunotherapy for treating early-stage triple negative breast cancer (TNBC). This study focuses on whether the anthracycline-free treatment combined with pembrolizumab is at least as effective as the standard anthracycline-containing regimen in preventing breast cancer events. The trial also examines various secondary outcomes including pathological response, survival rates, safety, tolerability, patient-reported quality of life measures, and translational objectives related to tumor immune markers. Participants are randomly assigned to one of two treatment groups. The first group receives paclitaxel, carboplatin, and pembrolizumab intravenously followed by doxorubicin, cyclophosphamide, and pembrolizumab before surgery. The second group receives docetaxel, carboplatin, and pembrolizumab intravenously before surgery. After surgery, patients in both groups may continue pembrolizumab treatment. Blood samples may be collected throughout the trial for additional analyses. During the study, participants undergo multiple assessments including imaging, blood tests, and physical exams before starting treatment. Patient-reported outcomes such as fatigue and physical function are collected through questionnaires. Follow-up visits occur every six months for two years, then annually up to five years to monitor breast cancer event-free survival and overall health. Safety and quality of life are continuously evaluated, and banking of physical specimens is performed for future research.

Researchers are conducting a Phase 2 clinical trial to evaluate the safety and tolerability of BB-031 in patients who have experienced an acute ischemic stroke within the past 24 hours. This study involves patients with an anterior circulation ischemic stroke confirmed by neurovascular imaging. The trial aims to assess the effects of ascending doses of BB-031 and selected doses compared to placebo in these patients. The study has two parts: Part A will enroll up to 48 participants randomized in a 3:1 ratio to receive one of three ascending dose levels of BB-031 or placebo to determine the appropriate doses for Part B. Based on safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy data from Part A, two dose levels will be selected for Part B. In Part B, approximately 180 participants will be randomized to receive a single dose of one of the two selected BB-031 doses or placebo. All treatments are given as a solution for injection. Participants will be followed for 90 days after receiving the study drug or placebo. Safety and radiological outcomes, including symptomatic intracranial hemorrhage within 24 hours, will be evaluated by a central blinded reviewer. A Data Safety Monitoring Committee will continuously review safety and preliminary efficacy data throughout the study to ensure participant well-being.