Marysville

Researchers are evaluating the effects of adding cemiplimab, an immunotherapy drug that blocks the PD-1 pathway to help the immune system attack tumor cells, to the usual treatment of docetaxel and ramucirumab in patients with stage IV or recurrent non-small cell lung cancer. This phase II/III Expanded Lung-MAP trial compares cemiplimab combined with docetaxel and ramucirumab versus docetaxel and ramucirumab alone, aiming to improve treatment outcomes in patients who previously received platinum chemotherapy and immunotherapy but developed resistance or disease progression. Participants are randomly assigned to one of two treatment arms. In Arm I, patients receive dexamethasone orally twice daily on days 0-2, ramucirumab and docetaxel intravenously on day 1 of each 21-day cycle. In Arm II, patients receive the same treatments plus cemiplimab intravenously on day 1 of each cycle. Treatment cycles continue every 21 days until disease progression or unacceptable side effects occur. Throughout the study, patients undergo regular blood sample collection and imaging scans such as CT or MRI to monitor disease status. During the study, participants are closely monitored with scans, blood tests, and physical exams to assess overall survival and other outcomes like progression-free survival, response rates, and treatment safety. Researchers also collect blood samples for future molecular studies. After completing treatment, patients are followed up every 3 to 6 months for up to 3 years to track long-term survival and health status. The study measures overall survival from randomization to death from any cause, assessed up to 3 years.

The goal of this trial is to determine the efficacy of advanced cognitive training for cancer survivors suffering from cancer- and cancer-treatment-related cognitive dysfunction. For millions of cancer survivors, cognitive dysfunction is a prevalent, severe, and persistent problem that has long been associated with poor work-related and health-related outcomes. Evidence suggests that a significant subset of breast cancer survivors (BCS) incur cognitive changes that may persist for years after treatment. Unfortunately, the scientific basis for managing these cognitive changes is extremely limited. Available evidence from pilot studies, including our work, suggests that advanced cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples of BCS, or limited outcome measures. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-blind, randomized controlled trial is to conduct a full-scale efficacy trial to compare advanced cognitive training to attention control in BCS.

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 three different combinations of drugs to treat newly diagnosed multiple myeloma in patients who are considered frail or intermediate-fit and are not eligible for stem cell transplant. This phase III trial focuses on comparing these three-drug induction treatments followed by either double- or single-drug maintenance therapy. The study aims to determine which treatment combination better controls the disease and improves progression-free survival and overall survival. Patients are randomly assigned to one of three treatment groups. Arm 1 (VRd-Lite) receives bortezomib by injection under the skin, lenalidomide by mouth, and dexamethasone by mouth during induction cycles, followed by lenalidomide alone for maintenance. Arm 2 (DRd-R) receives daratumumab and hyaluronidase-fihj injections, lenalidomide, and dexamethasone during induction, followed by lenalidomide alone during maintenance. Arm 3 (DRd-DR) receives the same induction as Arm 2, but maintenance includes both daratumumab and lenalidomide. Induction cycles last up to 9 cycles of 28 days each, and maintenance cycles continue every 28 days if the disease does not progress or toxicity occurs. Participants undergo assessments including tumor evaluations, whole-body imaging, blood tests, and quality-of-life questionnaires. After completing treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years. Researchers will measure progression-free survival, overall survival, response rates, safety, minimal residual disease, and patient-reported health outcomes to understand the treatments' effects and support future care decisions.

Researchers are comparing two approaches of standard therapy for patients with stage II to IIIB non-small cell lung cancer (NSCLC) that can be surgically removed. This phase III trial evaluates whether giving chemotherapy and immunotherapy before and after surgery (perioperative) is more effective than giving the same treatments only after surgery (adjuvant). The study aims to find out which method leads to better event-free survival and overall survival over several years. Participants are randomly assigned to one of two groups. In the adjuvant group, patients have surgery first, followed by up to four cycles of platinum-based chemotherapy and up to one year of immune checkpoint inhibitor treatment if there is no disease progression or unacceptable side effects. In the perioperative group, patients receive chemotherapy combined with immune checkpoint inhibitors before surgery, then have surgery, and continue immune checkpoint inhibitor therapy for up to one year afterward. Chemotherapy drugs used may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, or vinorelbine, and immunotherapy drugs may include nivolumab, pembrolizumab, or atezolizumab. During the study, patients undergo imaging tests such as CT scans, MRI, or PET/CT scans to monitor their condition. After completing treatment, they are followed for up to 10 years with check-ups every six months. Researchers measure event-free survival at three years, overall survival up to 10 years, surgical outcomes, side effects, and other treatment-related factors to understand which approach offers better results for patients with resectable NSCLC.

Researchers are evaluating two digital mindfulness meditation programs to support mental health and well-being in younger breast cancer survivors who have elevated depressive symptoms. This phase III trial focuses on women diagnosed with breast cancer at age 50 or younger who have completed their main cancer treatments at least six months ago. The study aims to compare a live, instructor-led online program to a self-paced app-based program and also to explore factors that might influence how well these interventions work, including psychological distress levels and social factors like race and education. Participants will be assigned to one of three groups: a live online Mindful Awareness Practices (MAPs) program delivered over Zoom, a self-paced MAPs digital app, or a meditation-only control group. The live online program includes guided meditations, exercises to manage pain and emotions, and cultivating kindness, with daily home practice increasing from 5 to 20 minutes. The app program unlocks lessons sequentially as participants progress. Meditation use will be tracked across all groups to measure engagement. During the study, participants will report depressive symptoms two weeks after completing the intervention. Researchers will also collect information on emotion regulation strategies and social determinants of health, and monitor how much participants practice mindfulness to understand the programs' effects. The total intervention lasts six weeks, and participants must be able to use a digital device and communicate in English or Spanish. Safety and participation are closely monitored throughout the study.

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 how factors like age, gender, other medical conditions, and the type of immunotherapy affect the development of side effects in patients with malignant solid tumors receiving immune checkpoint inhibitor (ICI) therapy. The study aims to develop and validate a risk prediction model for serious immune-related side effects during the first year of ICI treatment. Additional goals include tracking the occurrence of various side effects, quality of life, patient-reported symptoms, and treatment patterns over 12 months, along with studying biological markers that may predict side effect risk. Participants will have tissue samples collected at the start of their cancer treatment and will complete questionnaires at baseline and at weeks 4, 12, 24, and 52. Blood samples may also be collected at multiple times during the study. The study focuses on patients receiving standard-of-care ICI therapy for solid tumors, without combination chemotherapy or other non-ICI treatments. During the study, participants will complete patient-reported outcome forms and health questionnaires to assess side effects and quality of life. Researchers will monitor the occurrence of severe immune-related side effects over 52 weeks and evaluate biological markers from blood and tissue samples. The study also assesses the use of electronic methods for collecting patient data. Total participation includes assessments over approximately one year following treatment start.

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 investigating brain excitability in adults with major depressive disorder to improve depression treatment. The study aims to establish reliable markers of prefrontal cortex excitability using a method called Targeting with Automated Real-time Guidance for Enhancing TEPs (TARGET). Participants include those diagnosed with moderate-to-severe depression and some neurosurgical patients with medication-refractory epilepsy undergoing intracranial monitoring. The study compares different types of single-pulse transcranial magnetic stimulation (TMS) applied to the left dorsolateral prefrontal cortex. These include active single-pulse TMS, sham TMS that mimics sensations without stimulating the brain, TARGET-optimized TMS with real-time adjustments based on EEG feedback, and non-optimized TMS with preset parameters. Participants undergo concurrent scalp EEG recordings, and neurosurgical participants also have intracranial EEG monitoring during stimulation. Participants are involved in sessions where TMS is delivered and brain responses are recorded using EEG or intracranial EEG. Researchers measure changes in brain signal amplitudes before and after stimulation at specific time points up to 6 hours. The study evaluates neural responses to understand brain excitability patterns. Safety and clinical responses are monitored throughout the study period, which includes baseline and post-stimulation assessments.