Goldsboro

Researchers are collecting long-term safety and effectiveness data for participants treated with ibrutinib, a first-in-class, orally taken medicine that targets Bruton’s tyrosine kinase. The study focuses on individuals who have already been treated with ibrutinib in prior studies and are continuing to benefit from the treatment. The goal is to provide ongoing access to ibrutinib while monitoring health outcomes over time. Participants will continue taking ibrutinib capsules once daily at the dose established in their previous study (ranging from 140 mg to 560 mg) until the doctor decides the treatment is no longer helping, the participant chooses to stop, or other specified reasons occur. Some participants may receive ibrutinib alone or in combination with nivolumab depending on their prior treatment. The study is open-label, meaning everyone knows the treatment being given. During the study, participants are regularly monitored for safety and disease changes through assessments and visits until they stop the study drug or move to other treatments. Researchers track side effects up to 30 days after the last dose and may analyze how the disease responds in combination with earlier study data. The study continues until all participants transition off study treatment or the sponsor ends the trial, ensuring ongoing care and data collection over time.

Researchers are evaluating nemtabrutinib compared with the investigator's choice of ibrutinib or acalabrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not previously received treatment. The study aims to determine if nemtabrutinib is not worse than ibrutinib or acalabrutinib in terms of objective response rate, and whether it is better in progression-free survival according to specific criteria. This is a Phase 3 randomized clinical trial sponsored by Merck Sharp & Dohme LLC. Participants will be randomly assigned to receive either nemtabrutinib or the investigator’s choice of ibrutinib or acalabrutinib, all given orally at specified doses. Treatments continue until the disease progresses, unacceptable side effects occur, or other discontinuation criteria are met. This study compares these treatments directly to assess their effects in first-line therapy for CLL/SLL. During the trial, participants will be regularly monitored for treatment response and disease progression using standardized criteria assessed by independent reviewers, over periods up to approximately 33 months for response and up to 104 months for progression-free survival. Researchers will also evaluate overall survival, duration of response, adverse events, and reasons for treatment discontinuation. Careful safety monitoring will be conducted throughout the study, which may last up to several years from treatment start.

Researchers are studying repotrectinib (TPX-0005) in adults and adolescents with advanced solid tumors that have specific gene rearrangements in ALK, ROS1, or NTRK1-3. The trial aims to find the safest and most effective dose in Phase 1, and then evaluate how well the drug works in Phase 2 across different patient groups with these gene changes. This includes patients with tumors that have spread and those with brain involvement, focusing on response rates and survival outcomes. The study involves oral doses of repotrectinib. Phase 1 includes dose escalation to determine dose-limiting toxicities, maximum tolerated dose, and recommended dose for Phase 2. A sub-study also examines drug interactions with midazolam. In Phase 2, participants are assigned to one of six groups based on their tumor type and prior treatments, including different lines of targeted therapy and chemotherapy. Treatments continue according to protocol with regular monitoring. Participants will have measurable tumors confirmed by imaging reviewed centrally. They undergo physical exams, lab tests, and safety assessments throughout the study. Researchers measure response rates, duration of response, progression-free survival, overall survival, and clinical benefit over several years. The study monitors drug levels in blood and evaluates safety closely. Participation may last years with follow-up to assess long-term outcomes and effects on brain metastases.

Researchers are evaluating treatments for patients with BRAF-V600 mutant melanoma that has spread to the brain. This phase II trial compares two combinations: encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab. The study aims to determine which approach is more effective at shrinking and controlling brain metastases, and it also examines survival, response rates, and treatment safety. Patients are randomly assigned to one of two treatment groups. One group takes encorafenib daily by mouth, binimetinib twice daily by mouth, and receives nivolumab through an intravenous (IV) infusion every 28 days. The other group receives nivolumab IV every cycle and ipilimumab IV over 30 minutes during the first four cycles, with cycles repeating every 21 days initially, then every 28 days. Treatment continues unless disease worsens or side effects become unacceptable. Participants undergo brain MRI scans before enrollment and throughout the study to assess tumor response using specific criteria. After completing treatment, patients are followed every six months for two years, then yearly up to three years. The study collects tissue, blood, spinal fluid, and stool samples for future research. Researchers monitor progression-free survival as the main outcome, along with overall survival, response rates, and treatment side effects.

Researchers are evaluating the effectiveness and safety of different ibrutinib treatment plans, alone or combined with venetoclax, for people with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. This Phase 2 study compares regimens where ibrutinib dosing is either proactively reduced or adjusted in response to side effects. The goal is to find the best way to customize treatment while monitoring responses and adverse events. Participants receive ibrutinib capsules daily for a lead-in period of three 28-day cycles. Starting with cycle 4, some groups add venetoclax tablets with a gradual dose increase over five weeks, continuing both drugs daily for 12 cycles, while others continue ibrutinib alone at either the full or a reduced dose until disease progression or unacceptable side effects. Four different treatment arms explore these variations, including fixed duration and continuous therapy options. During the study, participants undergo regular evaluations to monitor cancer response, side effects, and quality of life for up to five years. Assessments include imaging scans to measure lymph nodes, blood tests, and questionnaires about symptoms and fatigue. Researchers track outcomes like overall response rate, survival, adverse events, treatment adherence, and changes in health status over time to understand the impact of each treatment plan.

Researchers are evaluating how well active surveillance helps doctors monitor patients with low-risk germ cell tumors after surgical removal. The study also compares chemotherapy treatments using carboplatin versus cisplatin in pediatric, adolescent, and young adult patients with metastatic standard risk germ cell tumors. It aims to determine overall survival, event-free survival, and side effects such as hearing loss among these patients. The study includes patients with low-risk stage I ovarian immature teratoma or stage I non-seminoma or seminoma germ cell tumors who undergo observation. Patients with standard risk tumors are randomly assigned to receive one of four chemotherapy regimens combining bleomycin, etoposide, carboplatin, or cisplatin, given intravenously on specific days over cycles repeating every 21 days. Treatments continue for up to 3 or 4 cycles if no disease progression or unacceptable side effects occur. Throughout treatment and observation, patients undergo imaging scans, blood sample collection, tumor biopsies if needed, and pulmonary function tests. Participants will be followed with regular imaging and blood tests to monitor tumor response and recurrence, including CT, MRI, and chest x-rays. Follow-up visits occur every 2 months for the first year, then every 3 to 6 months through year 2, every 6 months for years 3 to 5, and annually up to 10 years. The study also assesses hearing outcomes, body composition, tumor marker decline, neuropathy, and serum microRNA over time to better understand treatment effects and patient quality of life.

Researchers are evaluating whether adding the immunotherapy drug durvalumab to the usual chemotherapy treatment can improve outcomes for adults with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial compares standard chemotherapy alone to chemotherapy combined with durvalumab. Previous evidence suggests patients with this specific cancer profile may respond better to chemotherapy and immunotherapy, so this study aims to see if durvalumab helps prevent cancer from returning. Participants are first screened with MammaPrint testing on tumor tissue to confirm MP2 status. Those eligible are then randomly assigned to one of two treatment groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide every 14 days for 4 cycles. The other group receives the same chemotherapy schedule plus durvalumab intravenously during specific cycles. Mammography is done during screening, and optional tumor tissue and blood samples are collected throughout the study. During the trial, participants undergo regular assessments including mammograms, tissue biopsies, and blood tests to monitor response and safety. Researchers measure event-free survival, pathologic complete response, residual cancer burden, distant relapse-free survival, and overall survival for up to 10 years after treatment. Quality of life is also evaluated through questionnaires during and after treatment. Participants are followed long-term to track outcomes and side effects.

Researchers are studying advanced stomach or esophageal adenocarcinoma to see if adding the drug nivolumab to the usual treatment of paclitaxel and ramucirumab improves outcomes for patients. This phase II/III trial compares the combination of nivolumab, paclitaxel, and ramucirumab with paclitaxel and ramucirumab alone. The study aims to assess progression-free survival and overall survival, while also evaluating response rates, disease control, safety, and quality of life. Participants are randomly assigned to one of two groups. One group receives nivolumab intravenously on day 1 of each 28-day cycle, along with ramucirumab on days 1 and 15, and paclitaxel on days 1, 8, and 15. The other group receives ramucirumab and paclitaxel on the same schedule without nivolumab. Treatments continue unless the disease progresses or unacceptable side effects occur. Patients may also have optional blood tests, CT scans, and MRIs during the study. Throughout the trial, participants undergo regular imaging scans and optional blood sample collection to monitor disease status. After treatment ends, follow-up visits occur at 30, 60, and 90 days, then every 6 months for up to 3 years to assess survival and health. Researchers also collect patient-reported outcomes related to symptoms and quality of life during the study period.

Researchers are evaluating the addition of olaparib, a targeted therapy that blocks the PARP enzyme involved in DNA repair, in patients with pancreatic cancer who have had surgery to remove their tumor and carry a mutation in BRCA1, BRCA2, or PALB2. This phase II trial aims to determine if olaparib can improve relapse-free survival compared to placebo after chemotherapy completion. The study also explores overall survival and differences based on mutation type and chemotherapy received. Participants are randomly assigned to one of two groups. One group receives oral olaparib twice daily for 28-day cycles, up to 12 cycles, while the other group receives a placebo on the same schedule. Throughout treatment, patients undergo CT or MRI scans and blood collection. After treatment, patients are followed for up to 10 years with regular visits to monitor health and disease status. During the study, participants complete imaging scans and blood tests to assess disease progression and treatment effects. Researchers track relapse-free survival from the time of randomization until disease recurrence or death, with assessments extending up to 44 months. Safety and survival outcomes are monitored for up to 10 years. Follow-up visits occur 30 days after treatment and then every 4 months in the first year, followed by every 6 months for years 2 through 10.

Researchers are evaluating the effects of combining two drugs, cabozantinib and nivolumab, in treating patients with advanced melanoma or squamous cell head and neck cancer that has spread to nearby tissues, lymph nodes, or distant parts of the body. This phase II study aims to understand how well patients can be grouped based on tumor biomarkers, specifically tumor mutational burden and tumor inflammation signature, and to see if these markers influence how the cancer responds to treatment. Participants receive nivolumab through an intravenous infusion on the first day of each 28-day cycle, while cabozantinib is taken orally every day. Treatment cycles continue for up to two years unless the cancer worsens or side effects become unacceptable. During the study, patients undergo CT or MRI scans and blood sample collections. Tumor biopsies are done at screening and optionally during follow-up. After treatment ends, patients are followed every 12 weeks for one year, then every six months for up to three years. Throughout the trial, researchers monitor tumor response, including shrinkage or stabilization, and assess safety and side effects. They measure how quickly biomarker results can be obtained, overall response rates, disease control, progression-free survival, and overall survival. Additional analyses aim to identify biomarkers that predict response and side effects. Participants are regularly evaluated through scans, blood tests, and biopsies to track their health and treatment effects over time.