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Researchers are conducting a phase III randomized, open-label, multicenter trial across several countries including Sweden, Norway, Finland, Denmark, Italy, Australia, and New Zealand. The study focuses on elderly patients with untreated diffuse large B-cell lymphoma (DLBCL), defined as patients aged 80 years or older, or those aged 75 years or older who are considered frail based on a simplified Comprehensive Geriatric Assessment. The trial aims to compare the effectiveness of two treatment regimens in this population. Participants are randomly assigned to receive either the standard R-miniCHOP treatment or an experimental R-pola-miniCHP regimen where vincristine is replaced with an immunoconjugate, polatuzumab vedotin. Both treatments involve cycles of drugs including rituximab, cyclophosphamide, doxorubicin, and prednisone, administered over 18 weeks. The trial includes a screening period lasting up to 4 weeks, followed by the active treatment phase, and then a follow-up period lasting up to 36 months after treatment completion. Throughout the study, participants will be monitored to measure progression-free survival over 2 years as the primary outcome. The study involves regular assessments including clinical evaluations and safety monitoring. Enrollment began in the first quarter of 2020, with the last patient visit expected by the first quarter of 2027, allowing for long-term observation of treatment effects and patient outcomes.

Researchers are evaluating the effectiveness, safety, and tolerability of a combination treatment including adagrasib, pembrolizumab, and platinum-doublet chemotherapy compared to a placebo combined with pembrolizumab and platinum-doublet chemotherapy. This study focuses on adults with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. The trial is a randomized, double-blind, phase 3 study designed to provide insights into treatment options for this specific lung cancer type. Participants receive either adagrasib plus pembrolizumab alongside platinum-doublet chemotherapy drugs such as carboplatin or cisplatin and pemetrexed, or they receive a placebo plus pembrolizumab and the same chemotherapy regimen. The dosages and schedules of these drugs are specified and administered on predetermined days. The trial compares these two treatment groups to understand better the impact of adding adagrasib to the existing pembrolizumab and chemotherapy treatment. Throughout the study, participants are closely monitored for progression-free survival and overall survival, assessed up to seven years using standardized criteria for tumor response. Regular imaging scans such as CT or MRI are used to measure disease status. Safety and tolerability are also evaluated during the study, with ongoing assessments to track adverse effects and treatment response. The total duration of follow-up allows for long-term observation of treatment outcomes and participant health.

Researchers are evaluating the safety, tolerability, recommended Phase 2 dose, and early effectiveness of the drug BGB-11417 used alone and combined with azacitidine in adults with certain blood cancers, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myelodysplastic/myeloproliferative neoplasm (MPN). This study is conducted in Phase 1b and Phase 2 to find the best dose and assess responses in these myeloid malignancies. Participants receive BGB-11417 orally in cycles of 28 days, with dosing schedules of 10, 14, 21, or 28 days depending on the study part. Azacitidine is given intravenously or by injection for 7 days, and posaconazole is taken orally for 8 days during the second cycle only. There are different study parts including dose finding and expansion phases, with treatments adjusted accordingly. During the study, participants are monitored for dose-limiting toxicities and treatment-emergent side effects over about 24 months. Researchers also measure the rates of complete remission and overall response in different patient groups. Blood samples are collected to study drug levels, and safety is closely observed throughout the treatment cycles. The study lasts up to two years to evaluate the effects and safety of these therapies in patients with these blood cancers.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are evaluating the effectiveness of zanubrutinib combined with anti-CD20 antibodies compared to lenalidomide plus rituximab (R2) in adults with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL). The study aims to measure progression-free survival using independent review committees and established lymphoma response criteria based on PET/CT and CT imaging. Participants will receive zanubrutinib orally either as 160 mg twice daily or 320 mg once daily in continuous 28-day cycles. In the zanubrutinib plus rituximab group, rituximab is given intravenously at 375 mg/m2 on Days 1, 8, 15, and 22 of Cycle 1 and Day 1 of Cycles 2 to 5, each cycle lasting 28 days. The comparator group receives lenalidomide orally at 20 mg daily on Days 1 to 21 of each 28-day cycle for 12 cycles, plus obinutuzumab intravenously at 1000 mg on Cycle 1 Days 1, 8, 15 and Cycles 2 to 6 Day 1. During the study, participants will undergo imaging assessments such as PET/CT and CT scans to evaluate disease progression. Researchers will monitor treatment response and safety over approximately 78 months. Progression-free survival is the primary outcome, measured by a blinded independent review committee. Participants are expected to have measurable disease and adequate organ function at enrollment, with ongoing assessments to track treatment effects and adverse events.

Researchers are evaluating the effectiveness and safety of plixorafenib, an oral drug, in people aged 10 years and older who have various types of cancers with specific BRAF genetic changes. These include locally advanced or metastatic solid tumors, primary central nervous system (CNS) tumors with BRAF fusions, and rare BRAF V600-mutated tumors such as melanoma, thyroid cancer, and recurrent CNS tumors. The study is a Phase 2 Master Protocol designed to assess this targeted therapy in multiple subgroups based on tumor type and genetic profile. Participants receive plixorafenib oral tablets, and the study includes several subprotocols tailored to different tumor types and BRAF alterations. Subprotocols A, B, and C focus on tumors with BRAF fusions or rare BRAF mutations, while Subprotocol D enrolls adults aged 18 to 65 with solid tumors harboring BRAF V600E mutations not eligible for other subprotocols. Before starting treatment, participants provide tumor tissue or blood samples for genetic testing and scans to monitor tumor changes. Some subprotocols require stable or decreasing corticosteroid doses before treatment. Throughout the study, participants undergo regular evaluations including imaging scans, biopsies, and laboratory tests to assess tumor response and drug levels. The main outcomes measured are the objective response rate for most subprotocols and pharmacokinetics for Subprotocol D, with follow-up lasting up to approximately four years. Safety monitoring includes tracking adverse events and ensuring recovery from prior treatments, with additional assessments for heart function and infection status as needed.

Researchers are evaluating the maximum tolerated dose (MTD) and recommended combination dose of the PRMT5 inhibitor Anvumetostat when given with other therapies in adults with metastatic or locally advanced thoracic tumors that have a homozygous MTAP deletion. The study focuses on adults with thoracic tumors, including non-small cell lung cancer (NSCLC), to understand the safety and tolerability of these combinations. This is a Phase 1b study aiming to assess the safety profile of Anvumetostat combined with other treatments in this patient population. The study tests Anvumetostat administered orally alone or combined with intravenous therapies including carboplatin, paclitaxel, pembrolizumab, and pemetrexed, or oral sotorasib. Different treatment arms focus on specific histologies and biomarker statuses: one arm combines Anvumetostat with carboplatin, paclitaxel, and pembrolizumab for predominantly squamous NSCLC; another combines Anvumetostat with carboplatin, pemetrexed, and pembrolizumab for predominantly non-squamous NSCLC; a third arm combines Anvumetostat with pembrolizumab for PD-L1 positive tumors. A subgroup includes NSCLC patients with brain metastases meeting measurable disease criteria. Participants will be monitored for dose-limiting toxicities within approximately 21 days and for treatment-emergent and serious adverse events up to three years. Assessments include safety, tolerability, pharmacokinetics, and efficacy outcomes. Participants must provide tumor tissue samples or undergo biopsy if archival tissue is unavailable. The study evaluates disease status using RECIST v1.1 criteria and follows participants over time to track adverse events and treatment responses.

Researchers are evaluating whether fluid therapy using Plasma-Lyte48 compared to 0.9% sodium chloride can increase the number of days alive and days out of hospital by day 28 for critically ill patients with moderate to severe diabetic ketoacidosis (DKA) admitted to emergency departments and critical care areas. This phase 3, blinded, cluster crossover randomized controlled trial addresses the rising incidence and hospital admissions for DKA, aiming to provide definitive evidence to guide optimal fluid resuscitation. The study responds to current gaps in evidence and variability in DKA management protocols across hospitals in Australia. The trial involves 20 Australian hospitals participating in two 12-month intervention periods separated by a one-month gap. Each hospital uses either Plasma-Lyte48 or 0.9% saline as the blinded fluid therapy during the first period, then switches to the alternate fluid in the second period. Both fluids are supplied and labeled to preserve blinding, and clinicians administer the fluids based on standard clinical endpoints for up to 72 hours or until discharge from critical care. Additional treatments like glucose-containing solutions, bicarbonate, and electrolyte supplements are given as needed under clinician discretion. Participants will be monitored through the critical care stay and contacted by telephone at day 28 to assess outcomes. The main measurement is hospital-free days within 28 days after enrollment. The study also involves end-user representatives in all stages, ensuring consumer perspectives in protocol design and dissemination. This comprehensive approach aims to clarify the best fluid treatment for moderate to severe DKA and improve patient care and health outcomes.

Researchers are conducting LOCATOR, a multicenter phase II randomized clinical trial, to evaluate the quality of contouring in radiation treatment for breast cancer patients. The study compares artificial intelligence (AI) assisted contouring using the locally developed LOCATOR software with fully manual contouring done by radiation oncologists. The goal is to determine if AI-assisted contouring is as good as manual contouring and if it can save time for radiation oncologists. Participants are randomly assigned in a 3:1 ratio to receive either AI-assisted contouring or fully manual contouring. The AI model is initially trained on contours from 45 previous breast cancer cases and is updated regularly with new patient data. The AI generates initial contours automatically, which are then reviewed. The study also compares geometric accuracy, dosimetric differences, and economic factors between AI-assisted and manual contouring. Participants must be 18 years or older with primary breast cancer and able to consent. Researchers assess contour quality using the MD Anderson Contouring Grade Scale over 18 months, along with geometric and dosimetric evaluations. Safety and performance data are collected throughout the study, which includes ongoing updates to the AI model based on patient results.

Researchers are evaluating the long-term safety and effectiveness of pembrolizumab (MK-3475) in participants with advanced solid tumors or blood cancers who have previously taken part in other pembrolizumab-based studies. This phase 3 study includes participants who are either currently on treatment or in follow-up from prior parent studies. It aims to understand how well pembrolizumab works over an extended period, up to approximately 10 years, by observing overall survival and safety outcomes. The study has three phases: First Course Phase, Survival Follow-up Phase, and Second Course Phase. Participants who were receiving pembrolizumab, pembrolizumab-based combinations, or lenvatinib in their parent studies will continue treatment in the First Course Phase, completing up to 35 doses every 3 weeks or 17 doses every 6 weeks. Those in the Follow-up Phase will enter the Survival Follow-up Phase without additional treatment but will be monitored. Participants eligible for a Second Course Phase, who have not received other anticancer treatments since their prior pembrolizumab dose and meet health criteria, may receive up to 17 doses every 3 weeks or 8 doses every 6 weeks of pembrolizumab or its combinations. Some may also receive other study drugs such as olaparib, MK-4280, MK-4280A, or pembrolizumab with berahyaluronidase alfa. Participants will be involved in regular treatment visits, safety checks, and long-term monitoring for up to about 10 years to assess overall survival. Researchers will evaluate clinical outcomes, monitor any side effects, and check organ function and physical health status. The study includes detailed eligibility screening, including physical assessments and adherence to contraception requirements for women of childbearing potential. Safety follow-up is ongoing to ensure participant well-being throughout the study.