Colchester

This research aims to collect long-term safety and effectiveness data for participants treated with ibrutinib, a medicine used for various blood cancers and conditions including Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Diffuse Large B-cell Lymphoma, Waldenstrom Macroglobulinemia, and Chronic Graft Versus Host Disease. It also provides ongoing access to ibrutinib for participants who have completed previous ibrutinib studies, continue treatment, and benefit from it. This is an open-label Phase 3b study without formal hypothesis testing. Participants will continue their current ibrutinib dosing regimen from the prior study, taken orally once daily as capsules in doses of 560 mg, 420 mg, 280 mg, or 140 mg, around the same time each day. Treatment continues until the investigator decides the participant no longer benefits due to disease progression or side effects, the participant withdraws, alternative ibrutinib access becomes available, or the study ends. Participants not able to access ibrutinib elsewhere can keep receiving the single-agent ibrutinib until all transition or stop treatment, or until the study is stopped. During the study, safety is monitored throughout and summarized, and effectiveness may be analyzed together with previous study data. The main outcome measured is the number of participants experiencing any adverse events within 30 days after the last dose or until starting another cancer treatment. Participants will undergo assessments including pregnancy testing and investigator evaluations to ensure ongoing benefit and safety. The study duration depends on when participants stop treatment or transition to other access.

Researchers are evaluating whether reducing the frequency of pembrolizumab treatment after six months of standard therapy is safe and effective for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab, an immunotherapy targeting the PD-1 receptor on T cells, has improved outcomes for this condition. Because pembrolizumab remains bound to its target for a long time and dosing frequency may not affect outcomes, this study aims to find out if less frequent dosing can maintain effectiveness while reducing overtreatment and side effects. This phase III study also considers potential benefits like cost savings and improved quality of life due to fewer hospital visits. Participants who have completed six months of pembrolizumab treatment without disease progression and are continuing therapy will be randomly assigned to receive pembrolizumab at the standard six-week interval or at a reduced frequency of 12 weeks. If early results show that the 12-week schedule is not less effective, later participants may be randomized to even longer intervals of 9, 15, or 18 weeks. Pembrolizumab is given intravenously at 400 mg per dose. Patients whose disease progresses on a reduced frequency schedule may return to the standard six-week treatment. During the study, researchers will monitor overall survival at two years after randomization. Participants will undergo regular assessments to track disease status, treatment tolerability, and overall health. The study aims to confirm that less frequent dosing does not reduce survival while potentially improving patient experience. The trial is open to adults aged 18 and older with advanced NSCLC who have already completed six months of pembrolizumab therapy and intend to continue treatment.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole compared to placebo plus CDK4/6i and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. It aims to assess treatment outcomes in the first-line setting for this specific breast cancer type. Participants will be assigned to receive either oral inavolisib once daily or a matching oral placebo once daily. All participants will also receive a CDK4/6 inhibitor on either Days 1-21 or Days 1-28 of each 28-day cycle, along with daily oral letrozole. This randomized, double-blind study will compare these two treatment combinations to monitor differences in disease progression and safety. Throughout the study, researchers will evaluate progression-free survival from the time of randomization until disease progression or death, up to 7 years. Participants will undergo assessments including tumor measurements by RECIST criteria, performance status evaluations, and monitoring of blood and organ function before treatment begins. Safety and efficacy will be closely observed during treatment, aiming to provide detailed long-term data on the study therapies.

Researchers are evaluating the combination of bleximenib, venetoclax (VEN), and azacitidine (AZA) compared to placebo with venetoclax and azacitidine alone in treating adults newly diagnosed with acute myeloid leukemia (AML) who have specific gene mutations (NPM1 or KMT2A) and are not eligible for intensive chemotherapy. This is a phase 3 randomized, double-blind, placebo-controlled study focusing on participants with AML harboring these genetic abnormalities. The study aims to assess treatment effectiveness by measuring complete remission rates and overall survival. Bleximenib and venetoclax are given orally, while azacitidine is administered either intravenously or under the skin. Participants will receive either the combination of bleximenib, venetoclax, and azacitidine or placebo with venetoclax and azacitidine, following a rigorous treatment schedule. The study includes an initial treatment period where the effects of these drugs are compared to determine their impact on AML with the given mutations. Participants will be closely monitored through regular assessments, including evaluations of remission status and survival over a period of up to 4 years and 1 month. Safety and treatment responses will be tracked throughout the study. Participants must consent to follow the study procedures and agree to contraception requirements during and after treatment. The trial involves continuous observation to gather comprehensive data on treatment outcomes and participant health.

Researchers are investigating preventive treatments to reduce the occurrence, severity, and duration of taste changes (dysgeusia) related to talquetamab and ramantamig in patients with multiple myeloma. This Phase 2 open-label study aims to better understand the signs and symptoms of these oral events during a preventive treatment phase. Participants have multiple myeloma and have previously received specific prior therapies. The study involves several treatment options, including talquetamab and ramantamig, both given by subcutaneous injection, along with four different prophylaxis treatments (Prophylaxis A, B, C, and D) administered either orally or topically. These treatments are evaluated during the prophylaxis phase lasting up to 12 months. The goal is to assess how well these interventions prevent taste changes associated with talquetamab. Participants will be monitored for the presence and severity of taste changes through a standardized taste test called the Total Waterless Empirical Taste Test (WETT). Researchers will measure the percentage of participants experiencing dysgeusia, time to onset of severe taste changes, and the percentage reporting improvement or resolution at specific time points during the 12-month prophylaxis phase. Safety and adherence to lifestyle guidelines are also part of the participant evaluations throughout the study.

Researchers are evaluating the efficacy and safety of inavolisib combined with Phesgo compared to placebo with Phesgo as maintenance therapy in participants who have previously untreated HER2-positive advanced breast cancer with PIK3CA mutations. This Phase III, multicenter, randomized, double-blind, placebo-controlled study focuses on participants with locally advanced or metastatic breast cancer, aiming to understand the treatment impact after initial induction therapy. Participants will receive inavolisib orally once daily on Days 1 to 21 of each 21-day cycle, starting on Day 1 of Cycle 1 during maintenance treatment. Phesgo will be administered subcutaneously every three weeks on Day 1 of each cycle. The study includes an induction therapy phase where taxane-based chemotherapy is given after Phesgo. Optional endocrine therapy such as tamoxifen, aromatase inhibitors, or fulvestrant may be used based on the investigator's choice, with luteinizing hormone-releasing hormone agonists administered according to local guidelines. During the study, participants will be monitored for progression-free survival for up to approximately 40 months. Assessments include evaluation of heart function, organ function, and overall health status. Researchers will track the safety and effectiveness of the treatment combination through regular clinical evaluations and laboratory tests. The total duration includes maintenance treatment cycles and follow-up to measure outcomes and monitor safety.

Researchers are evaluating treatment options for patients with early-stage classical Hodgkin lymphoma who have not received prior therapy. This international phase III trial runs two parallel studies in different regions, combining data to better understand treatment effects. The trial compares two chemotherapy regimens, ABVD and A2VD, with treatment adapted based on PET-CT scan results after two cycles to guide further therapy. Participants will be randomly assigned to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine, and dacarbazine with growth factor support). PET-CT scans are performed after one cycle for exploratory purposes and after two cycles to determine subsequent treatment. Depending on PET results, patients may receive additional chemotherapy cycles or involved site radiotherapy following ILROG guidelines. Those with poor response discontinue trial treatment and receive alternative therapy. During the study, patients undergo PET-CT scans and regular assessments to monitor treatment response and safety. Follow-up continues for at least five years after treatment completion to assess progression-free survival. Researchers collect clinical data and imaging results to evaluate outcomes, with central review of PET scans guiding treatment adaptations. Participants are monitored for side effects and overall health throughout the trial period.

Researchers are evaluating two surgical approaches for patients with low risk differentiated thyroid cancer in this multi-center, randomized, phase III study. The study aims to determine if hemithyroidectomy, which removes part of the thyroid, is an acceptable and cost-effective alternative to total thyroidectomy, which removes the entire thyroid. Patients are identified through oncology multidisciplinary team meetings and divided into two groups based on their treatment history and diagnosis method. Patients in Group 1 have already had a hemithyroidectomy for thyroid problems and are then diagnosed with low risk differentiated thyroid cancer. They will be randomized to either surveillance only or a second surgery to remove the rest of the thyroid gland (two-stage total thyroidectomy). Group 2 patients are diagnosed by cytology with low risk cancer and have not yet had surgery; they will be randomized to either hemithyroidectomy or a single-stage total thyroidectomy. The study plans to recruit 456 patients who will be followed after surgery and then every 12 months for 6 years. During the study, participants will undergo regular assessments to monitor for any signs or symptoms of cancer recurrence, with a primary outcome measure of the 3-year recurrence rate after surgery. Follow-up visits will include clinical evaluations to check for cancer return or progression. Researchers will also observe overall patient outcomes and safety throughout the 6-year follow-up period.

Researchers are evaluating whether online patient education is a practical option for people aged 18 to 44 with patellofemoral pain (pain around or behind the kneecap) who are waiting for physiotherapy. This feasibility trial aims to see if patients will accept and stick to the online education and to gather data to guide a larger future study. The study invites participants already on a physiotherapy waiting list and confirms their diagnosis through a face-to-face assessment before randomizing them to different groups. Participants are assigned to one of two groups. The first group receives access to an online education platform with four modules that teach about understanding pain, starting exercises, treatment options, and case studies. They are encouraged to complete one module per week and take quizzes to track engagement. Those without internet access get a paper version. The second group receives usual care and no extra education during the six-week waiting period but may access the education platform afterward if requested. Throughout the six weeks, researchers monitor recruitment, adherence to the education, participant feedback, and completion of questionnaires measuring pain, quality of life, and overall change. Data collection is done through a secure system, with support for those less comfortable with digital tools. Selected participants in the online education group may join focus groups or interviews to share their experiences and discuss the impact of the education and ongoing physiotherapy needs.

Researchers are investigating the use of Magnetic Resonance Tumour Regression Grade (mrTRG) as a new imaging biomarker to guide treatment decisions in patients with locally advanced rectal cancer. This phase III trial in the UK is unique in offering a 'watch and wait' approach for patients who respond well to pre-operative treatment, potentially avoiding surgery and preserving quality of life. The study aims to validate mrTRG to differentiate between good and poor responders to radiotherapy and help tailor ongoing treatment and surveillance accordingly. Participants will be randomly assigned to one of two groups. The control group will receive standard management based on national guidelines and clinical assessments after treatment, including routine MRI scans without mrTRG reporting. The intervention group will have post-treatment MRI scans evaluated by specially trained radiologists to assess mrTRG grades. Patients classified as good responders (mrTRG 1 or 2) will be offered a watch and wait approach to avoid surgery, while poor responders (mrTRG 3 to 5) will have their cases reviewed by a local colorectal multidisciplinary team for further treatment planning. During the study, all participants will undergo routine MRI scans following standardized protocols and complete quality of life questionnaires at registration, 3 years, and 5 years. Researchers will monitor outcomes for up to five years, focusing on whether surgery can be safely avoided in good responders and tracking long-term effects on health and survival. The study does not mandate specific chemotherapy or investigational treatments, allowing local teams to decide additional therapy as needed.