Stoneham

This research evaluates the combination of two drugs, cabozantinib and nivolumab, in treating patients with advanced melanoma or squamous cell cancers of the head and neck that have spread locally or to distant parts of the body. The study focuses on how well patients can be grouped based on specific tumor biomarkers called tumor mutational burden and tumor inflammation signature. It also aims to understand if this drug combination can shrink or stabilize tumors and how responses vary with biomarker status. This is a phase II trial assessing both the feasibility of biomarker-based patient grouping and the treatment's overall response rate. Participants receive nivolumab intravenously once every 28-day cycle and take cabozantinib orally every day for up to two years unless the disease worsens or side effects become unacceptable. The study includes two stages focusing on molecular characterization and treatment efficacy. Patients undergo tumor biopsies at screening and optionally during follow-up, along with regular imaging scans like CT or MRI and blood sample collections throughout the study. During the trial, patients are closely monitored through scans, blood tests, and biopsies to track tumor response and safety. After treatment ends, follow-up visits occur every 12 weeks for one year and then every six months for up to three years. Key outcomes include the time to get biomarker results within 21 days and the overall tumor response rate at the end of the first stage. The study also assesses disease control, progression-free survival, overall survival, and safety of the drug combination in relation to tumor biomarkers.

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 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 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 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 investigating whether observation is as effective as continuing pembrolizumab treatment in patients with early-stage triple-negative breast cancer who achieved a complete response after preoperative chemotherapy combined with pembrolizumab. This phase III trial aims to evaluate recurrence-free survival and quality of life, as well as the value of reducing immunotherapy treatment after surgery in these patients. The study also examines differences in adverse events, overall survival, and financial impacts between treatment approaches. Participants are randomly assigned to one of two groups after completing neoadjuvant chemotherapy with pembrolizumab and surgery. One group receives pembrolizumab intravenously as adjuvant therapy, while the other group undergoes observation without further treatment. Both groups have tumor biopsies and blood samples collected on study and during follow-up. Additional assessments include questionnaires and quality-of-life evaluations. During the study, researchers monitor participants for up to 10 years to measure recurrence-free survival. They assess quality of life using validated tools, track adverse events, and evaluate financial toxicity and work productivity. The study includes tumor tissue analysis, blood sample collection, and patient-reported outcomes to understand the long-term effects and value of treatment de-escalation in breast cancer care.

Researchers are collecting real-world data on patients with advanced Epidermal Growth Factor Receptor (EGFR)-mutated Non-Small Cell Lung Cancer (NSCLC) who are treated outside of clinical trials. The study aims to better understand the safety and effectiveness of standard care treatments involving osimertinib alone or combined with chemotherapy. This observational study includes patients from both academic and community medical centers to reflect routine clinical practice. The study compares two treatment groups: one receiving osimertinib as a single oral daily dose, and another receiving osimertinib plus chemotherapy, with the chemotherapy regimen chosen by the treating physician. Treatment dosing and administration follow standard care guidelines or institutional protocols. The decision on which treatment a patient receives is made by their doctor and recorded when the patient joins the study. Participants will be followed as per their physician's usual care, including clinical and imaging assessments. Researchers will track progression-free survival, measuring the time from starting therapy until disease progression or death, for up to three years. The study plans to enroll up to 538 patients, with about 250 in each treatment group, to evaluate outcomes and monitor safety in a real-world setting.

Researchers are evaluating targeted therapy directed by genetic testing for patients with locally advanced or advanced solid tumors that have spread to nearby tissues, lymph nodes, or other parts of the body. This research focuses on patients whose cancer has progressed despite standard treatments or for whom no standard treatment has been shown to improve survival. The trial aims to match patients to treatments based on specific genetic changes in their tumor cells, in hopes of controlling the tumor and improving treatment planning. This effort is part of the ComboMATCH program, a coordinated set of clinical trials designed to study combination therapies targeting molecularly defined patient groups. Patients undergo tumor mutational screening using previously collected samples, and those 18 years or older with disease suitable for biopsy may have a new tumor biopsy before starting treatment. Participants are assigned to one of multiple treatment subprotocols based on their tumor's genetic mutations. Treatments include various drugs taken orally, intravenously, or by injection, such as selumetinib, olaparib, fulvestrant, paclitaxel, and others, often in combination. Treatment cycles typically repeat every 28 days unless disease progression or unacceptable side effects occur. Some patients may be randomized to different treatment arms, and crossover to other arms is sometimes allowed. Procedures also include biopsies, blood collection, imaging scans (CT, MRI, PET), bone marrow aspiration, and heart function tests throughout the study. Participants are closely monitored with scans, biopsies, blood tests, and heart evaluations during treatment to assess response and safety. These assessments occur at various times, including screening, during treatment cycles, and follow-up periods that can last up to several years. Researchers measure patient enrollment rates, assignment to treatment arms, and outcomes within defined patient groups. The study also compares tumor genetic profiles from tissue and blood samples to better understand responses. Overall, the trial provides long-term observation of patients receiving personalized targeted therapies based on genetic testing results.

Researchers are evaluating whether starting treatment early with venetoclax and obinutuzumab improves overall survival compared to delayed treatment in patients newly diagnosed with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This phase III trial focuses on patients who have asymptomatic disease but high-risk factors such as a high CLL-International Prognostic Index score or complex cytogenetics. Venetoclax is a drug that blocks a protein needed for cancer cell survival, while obinutuzumab is an immunotherapy that may help the immune system attack cancer cells and prevent tumor growth. Participants are randomly assigned to one of two groups: early treatment or delayed treatment. Both groups receive obinutuzumab intravenously on specific days in cycles and venetoclax orally daily during treatment cycles, with each cycle lasting 28 days for up to 12 cycles unless the disease progresses or unacceptable side effects occur. The early treatment group starts therapy as soon as they meet eligibility, while the delayed group begins once standard criteria for active treatment are met. Throughout the study, participants undergo procedures including CT scans, blood sample collection, and bone marrow aspiration and biopsy. During the study, participants are monitored closely through various tests and questionnaires to assess overall survival, quality of life using the FACT-Leukemia scale, response to treatment, and disease progression. The trial also studies measurable residual disease and various biomarkers to understand treatment impact. After treatment, participants are followed for up to 10 years to observe long-term outcomes and safety.

Researchers are evaluating a phase II clinical trial comparing two targeted treatment approaches in women with recurrent or persistent ovarian, fallopian tube, primary peritoneal, or endometrial cancers that have mutations in the RAS pathway. The study tests the combination of selumetinib and olaparib versus selumetinib alone. Selumetinib blocks enzymes needed for tumor cell growth, while olaparib inhibits an enzyme that repairs damaged DNA, potentially increasing tumor cell death. The study aims to assess whether adding olaparib improves tumor shrinkage and lengthens the time tumors remain stable compared to selumetinib alone. Participants are assigned to one of two groups: one receives both selumetinib and olaparib orally twice daily in 28-day cycles, while the other receives selumetinib alone with the option to switch to combination therapy if the disease progresses. Patients undergo tumor biopsies and blood collections during screening and treatment. Regular imaging tests, such as CT scans and heart function tests (ECHO or MUGA), monitor disease status and safety. Bone marrow samples may be taken if needed. Treatment continues until disease worsens or unacceptable side effects occur. During the study, participants are closely monitored with scans and lab tests to evaluate tumor response and safety. After treatment ends, follow-up visits occur every 3 months for 2 years, then every 6 months for 3 more years to track progression-free survival and long-term outcomes. The trial also collects tissue samples to analyze genetic profiles related to treatment response and resistance.