Norwich

Researchers are evaluating a blood-based test called Episwitch CiRT4 to see if it can predict how patients with stage III or IV cancer will respond to immune checkpoint inhibitor ICI treatments, specifically PD-L-1 inhibitors. This observational study aims to compare test predictions with actual patient responses across different types of cancer. The study also explores how social factors might relate to treatment responses and outcomes. Patients who are candidates for or currently receiving ICI therapy will undergo the Episwitch CiRT4 test before starting or during treatment. If the test indicates a high likelihood of response, repeat testing will occur every three months. Participants will be followed for six months to collect data on treatment administered, disease progression, survival, and patient-reported outcomes, along with social determinants of health. Throughout the study, researchers will gather clinical information, including physician questionnaires and patient feedback, to assess outcomes such as disease-free survival and time to recurrence. The study will also analyze health economics related to the tests potential to reduce unnecessary ICI treatments. Monitoring will continue for 24 weeks, with comprehensive data collection to evaluate the correlation between test results, social factors, and patient outcomes.

Researchers are comparing the effectiveness of a combination treatment including tarlatamab, durvalumab, carboplatin, and etoposide to a similar combination without tarlatamab in people with untreated extensive stage small-cell lung cancer ES-SCLC. This Phase 3 study aims to see if adding tarlatamab can improve overall survival and progression-free survival in this patient group. The study is sponsored by Amgen and focuses on first-line treatment options for this aggressive cancer stage. Participants are assigned randomly to one of two groups. One group will receive tarlatamab combined with durvalumab, carboplatin, and etoposide for four cycles, followed by maintenance treatment with tarlatamab and durvalumab. The other group receives durvalumab, carboplatin, and etoposide for four cycles, followed by durvalumab alone. All drugs are given through intravenous infusions. The study is open-label, meaning both participants and researchers know which treatment is being given. During the study, participants will be monitored up to approximately 3.5 years for overall survival and progression-free survival through blinded independent central review. Additional outcomes like objective response, disease control, duration of response, and treatment-related side effects will be tracked for up to four years. Blood samples will be taken to measure tarlatamab levels and to check for antibodies against the drug. Safety and treatment effects are carefully recorded throughout the study period.

Researchers are evaluating the safety and effectiveness of various targeted therapies and immunotherapy combinations in adults with metastatic colorectal cancer mCRC whose tumors show specific biomarkers. This open-label, exploratory Phase 1 study aims to understand how these treatments work in different patient subgroups based on their tumors genetic characteristics. Participants are assigned to treatment groups depending on their biomarker test results. Participants receive different combinations of drugs such as inavolisib, cetuximab, bevacizumab, atezolizumab, tiragolumab, SY-5609, divarasib, FOLFOX, and FOLFIRI. Treatments may be given orally or by intravenous infusion following specific schedules, with cycles lasting 21 or 28 days depending on the regimen. Some treatment arms are closed, while others are active or recruiting participants. Throughout the study, participants undergo regular assessments including tumor measurements to evaluate response rates. Researchers monitor safety by tracking adverse events and measure drug levels in the blood at set intervals. The primary outcome is the objective response rate over approximately 84 months, with secondary outcomes including duration of response, disease control rate, and recommended doses for some drug combinations. The study lasts several years, with ongoing monitoring of participants health and tumor status.

Researchers are evaluating treatments for participants with KRASNRAS and BRAF wild-type colorectal cancer that is recurrent, unresectable, or metastatic. The study compares the length of time participants remain disease-free and overall survival when treated with amivantamab plus chemotherapy versus cetuximab or bevacizumab plus chemotherapy. All participants have previously received chemotherapy, and the study is a randomized, open-label phase 3 trial sponsored by Janssen Research Development, LLC. Participants are assigned to one of two groups. One group receives amivantamab combined with the FOLFIRI chemotherapy regimen, which includes 5-fluorouracil, leucovorin calcium or levoleucovorin, and irinotecan. The other group receives either cetuximab or bevacizumab combined with FOLFIRI. Treatments are given in 28-day cycles and continue until the disease progresses or other reasons require stopping treatment. During the study, participants undergo regular assessments including imaging to monitor disease status and response to treatment. Researchers measure progression-free survival, overall survival, response rates, duration of response, and quality of life through questionnaires. Safety is monitored by tracking adverse events and laboratory test changes. The primary outcomes are evaluated up to about 2 years for progression-free survival and over 4 years for overall survival, with several secondary outcomes assessed up to the same longer timeframe.

Researchers are evaluating nemtabrutinib compared with the investigators 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 investigators 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 CLLSLL. 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.

This trial investigates whether adding intismeran autogene to pembrolizumab after surgery can help people with non-small cell lung cancer NSCLC remain cancer-free longer than those receiving pembrolizumab with a placebo. It focuses on patients whose tumors did not completely respond to treatment before surgery. The study is a Phase 3, randomized, double-blind trial assessing adjuvant therapy following neoadjuvant treatment and surgery in resectable Stage II to IIIB NSCLC without complete pathological response. Participants first receive neoadjuvant treatment with pembrolizumab and chemotherapy every 3 weeks for up to 4 cycles, lasting about 12 weeks. After surgery, they get adjuvant treatment with pembrolizumab every 6 weeks for up to 7 cycles, combined with either intismeran autogene or placebo given by intramuscular injection every 3 weeks for up to 9 doses, for a total of about 42 weeks. The study compares these two groups to evaluate the impact on cancer recurrence. During the trial, participants undergo regular evaluations including disease-free survival monitoring for up to approximately 97 months, and other measures like overall survival, metastasis-free survival, and quality of life assessments for up to around 129 months. Safety is tracked by recording adverse events and therapy discontinuations. Follow-up involves questionnaires and clinical tests to assess health status and treatment effects over the long term.

Researchers are evaluating different treatment combinations for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma CLLSLL. This phase 3 study compares how well sonrotoclax combined with either obinutuzumab or rituximab works against venetoclax plus rituximab. The study also monitors the safety of these treatments as part of the comparison. Participants will receive one of four treatment combinations sonrotoclax with obinutuzumab, sonrotoclax with rituximab, sonrotoclax with obinutuzumab guided by minimal residual disease evaluation, or venetoclax with rituximab. Sonrotoclax and venetoclax are given orally, while obinutuzumab and rituximab are given intravenously. Treatment continues with evaluations based on disease response and minimal residual disease status. During the study, participants will have regular assessments including disease progression, response rates, overall survival, quality of life, and safety monitoring. These assessments include clinical evaluations, laboratory tests, and quality of life questionnaires. The primary outcome is progression-free survival up to about 51 months, with other outcomes assessed up to 84 months. Participants are monitored from study start through treatment and follow-up periods, which may last several years.

Researchers are evaluating the effectiveness of the Change4Better C4B mobile app in reducing the severity of problem gambling compared to standard treatment as usual TAU. This study is a 6-month randomized clinical trial involving individuals with gambling disorder who are enrolled in or seeking treatment at outpatient facilities affiliated with Bettor Choice Gambling Treatment Programs or Kindbridge Behavioral Health. The study aims to assess the feasibility and efficacy of adding the C4B app, which is based on cognitive behavioral therapy, as a support tool alongside routine outpatient treatment. Participants will be randomly assigned to one of two groups one group will receive standard TAU, which includes individual or group therapy sessions tailored to their needs and usually lasts about one hour per week for 12 weeks. The other group will receive TAU plus access to the C4B mobile app, which teaches skills to manage gambling behaviors and cognitive distortions. Participants using the app will be instructed by staff on how to use it and encouraged to spend about 8 hours over 12 weeks completing modules and practicing exercises. Monthly follow-up continues for an additional 12 weeks, during which the app remains accessible. During the study, participants will be monitored for changes in gambling symptom severity from baseline to 6 months. Researchers will track app engagement through measures such as days used, topics completed, practice exercises, weekly usage, and total time spent. Participants will continue receiving usual outpatient care, and data will be collected through assessments and follow-ups conducted by the Yale research team. The total study duration for each participant is 6 months, starting from randomization.

Researchers are studying patients with non-small cell lung cancer NSCLC to better understand how the cancer changes on a molecular level during standard treatments. The study aims to track the diseases progress and explore how changes in circulating tumor DNA ctDNA might predict cancer recurrence and treatment outcomes. This observational study collects clinical and molecular health data over time from patients receiving usual care. The study involves two groups of patients. The first group includes patients with early-stage NSCLC Stages I to IIIB who are treated with surgery and possibly additional therapies before or after surgery. The second group includes patients with advanced stage IV NSCLC receiving first-line immunotherapy, either alone or combined with chemotherapy. Patients will provide blood samples regularly during their routine care to help researchers analyze ctDNA and its changes over time. Participants will be asked to provide tumor samples and give additional blood samples during standard surveillance visits. Researchers will monitor disease-free survival and overall survival over periods up to five years. They will also compare ctDNA testing results with traditional imaging methods used every six months to detect cancer recurrence. The study tracks various outcomes, including treatment patterns and progression-free survival, to gain a detailed understanding of how the disease evolves under standard care.

Researchers are evaluating the effectiveness and safety of Adagrasib MRTX849 alone and combined with pembrolizumab in patients with advanced non-small cell lung cancer NSCLC who have the KRAS G12C mutation. The study includes a Phase 2 portion focusing on patients with various PD-L1 scores and a Phase 3 portion comparing Adagrasib plus pembrolizumab versus pembrolizumab alone in patients with high PD-L1 levels. This research aims to improve first-line treatment options for advanced NSCLC. The Phase 2 study has three groups two cohorts with low PD-L1 scores receiving either Adagrasib alone or combined with pembrolizumab, and one cohort with higher PD-L1 scores receiving the combination. In Phase 3, patients are randomly assigned to receive either Adagrasib with pembrolizumab or pembrolizumab alone. Adagrasib is taken orally twice daily, while pembrolizumab is given by intravenous infusion every three weeks. Participants will undergo regular assessments over 22 months for Phase 2 and 36 months for Phase 3, including evaluations of tumor response, safety, quality of life, and drug levels in the blood. Brain imaging is also used to check for metastases. Researchers will monitor progression-free survival, duration of response, and side effects to understand the treatments impact and tolerability throughout the study period.