Easton

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 a new treatment approach for patients with locally advanced unresectable or metastatic renal cell carcinoma (RCC) in this Phase 3, randomized, double-blind, placebo-controlled study. The study compares the combination of the drug pazopanib with abexinostat against pazopanib with a placebo. The goal is to assess the effectiveness of adding abexinostat to pazopanib in treating this type of kidney cancer. Participants will be randomly assigned in a 2:1 ratio to receive either pazopanib plus abexinostat or pazopanib plus a placebo. Pazopanib is taken orally once daily at 800 mg each morning with water, timed around meals. Abexinostat or its placebo is taken twice daily at 80 mg on specific days within a 28-day treatment cycle, with doses spaced four hours apart and taken around meal times. Treatment will continue until disease progression, unacceptable side effects, withdrawal of consent, or study closure. Patients on placebo who experience disease progression may switch to the combination treatment. Before starting treatment, patients undergo screening within 28 days and receive their first dose within 7 days after randomization. Throughout the study, researchers monitor patients for progression-free survival, which is the time from randomization until disease progression or death, for up to about four years. Regular assessments include imaging scans evaluated by specific criteria, clinical evaluations, and safety monitoring. There is no set maximum treatment duration, allowing patients to continue therapy as long as it remains beneficial and safe.

Researchers are investigating the safety and effectiveness of crizanlizumab compared to a placebo in adolescents and adults aged 12 years and older who have Sickle Cell Disease and experience frequent vaso-occlusive crises (VOCs). This phase III, multicenter, randomized, double-blind study includes patients who have had between 4 and 12 healthcare professional-managed VOCs in the past year. Participants may or may not be taking hydroxyurea or hydroxycarbamide therapy alongside the study treatment. Participants will be randomly assigned in a 2:1 ratio to receive either crizanlizumab at a dose of 5 mg/kg or a placebo, both given as intravenous infusions. The randomization is stratified based on whether they are using hydroxyurea/hydroxycarbamide and by geographic region (South America, North America, and sub-Saharan Africa). Crizanlizumab and placebo are provided in single-use vials for infusion. Treatment will be monitored over a planned period of at least 52 weeks. Throughout the study, participants will be closely monitored for the number of VOCs that require healthcare professional management, including those handled in a healthcare facility or remotely, over one year. Medical history, laboratory tests, and other assessments will be used to document VOCs and evaluate safety. Participants who are on hydroxyurea/hydroxycarbamide or erythropoietin stimulating agents must maintain stable doses during the study. The study aims to assess both the rate of VOCs and the overall safety profile of crizanlizumab in this patient population.

Researchers are evaluating the safety and effectiveness of an experimental drug combination, fianlimab and cemiplimab, in adults with advanced or metastatic melanoma, a type of skin cancer. This phase 3 study compares this combination with an approved treatment using relatlimab and nivolumab (Opdualag14). The study also investigates possible side effects, drug levels in the blood, and whether the body produces antibodies that might affect the drugs' performance or safety. Participants receive either fianlimab and cemiplimab together through intravenous (IV) infusions every three weeks or the comparator drugs relatlimab and nivolumab by IV every four weeks. The treatment period is followed closely by researchers who monitor how participants respond to the therapies and how well they tolerate them. During the study, participants undergo regular assessments including scans and laboratory tests to measure tumor response using standardized criteria (RECIST 1.1). Researchers also monitor safety, immune response, and drug levels for up to 72 months. The study requires participants to have measurable melanoma and good organ function, and they are observed for overall treatment effects and side effects throughout the trial.

Researchers are investigating the addition of an immunotherapy drug called durvalumab to standard chemotherapy treatment in patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial aims to compare the effectiveness of usual chemotherapy alone versus chemotherapy combined with durvalumab. Immunotherapy with durvalumab may help the immune system attack cancer cells and prevent tumor growth and spread, while chemotherapy drugs like paclitaxel, doxorubicin, and cyclophosphamide work to stop cancer cells from growing or dividing. Previous studies suggest patients with an MP2 result might respond better to this combined treatment approach. Participants first undergo MammaPrint testing to confirm MP2 status before randomization into two groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide intravenously on day 1 every 14 days for 4 cycles. The other group receives the same chemotherapy schedule plus durvalumab intravenously over 60 minutes on specified cycles during both chemotherapy phases. Mammography is performed during screening, and optional tissue and blood samples are collected for future studies. Throughout the study, participants are monitored through various assessments including imaging, physical exams, laboratory tests, and quality of life questionnaires focusing on fatigue and physical and mental health. Researchers track breast cancer event-free survival and other outcomes such as treatment side effects and response rates. After completing treatment, patients are followed for up to 10 years or until death to evaluate long-term outcomes and safety.

Researchers are evaluating two different methods for monitoring pancreatic cysts to determine which approach leads to better outcomes for patients with these cysts. The study compares a lower intensity surveillance schedule with a higher intensity surveillance schedule in patients aged 50 to 75 years. The study also aims to assess differences in surgical complications, pancreatic cancer rates, mortality, costs, healthcare use, patient quality of life, anxiety, financial distress, adherence to surveillance, and the predictive value of biomarkers and radiomic markers for cancer or dysplasia. Participants are randomly assigned to one of two surveillance arms. In the low intensity arm, patients receive MRI or CT scans at the start and one year later, then repeat imaging every two years if no abnormalities are found. If positive features appear, imaging frequency increases. In the high intensity arm, surveillance frequency varies by cyst size, ranging from MRI or CT every six months to combined imaging and endoscopic ultrasound (EUS) every 3-6 months for larger cysts. EUS is used to further evaluate cysts based on size and findings. After imaging procedures, patients are followed for five years from enrollment. During the study, patients undergo procedures including MRI, CT, and EUS, along with quality-of-life and questionnaire assessments. Researchers will monitor clinical outcomes, imaging results, healthcare utilization, costs, patient-reported outcomes, and biomarker performance. Safety and adherence to surveillance schedules will be tracked. The study lasts five years after the initial registration to capture long-term outcomes related to pancreatic cyst monitoring.

Researchers are evaluating whether breast conservation surgery combined with endocrine therapy can achieve a similar rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation surgery followed by breast radiation and endocrine therapy in patients with Stage I, hormone sensitive, HER2-negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial builds on the established role of radiation after lumpectomy, aiming to identify if radiation can be safely omitted in certain low-risk patients to reduce treatment burden and side effects. Participants receive either breast radiation plus endocrine therapy or endocrine therapy alone. Radiation therapy involves external beam radiation to the whole breast with or without a boost, partial breast irradiation, or accelerated partial breast irradiation, starting within 12 weeks after the last breast surgery. Endocrine therapy is given for a minimum of 5 years, with the specific drug choice and schedule determined by the treating physician. Endocrine therapy may begin before, during, or after radiation therapy, depending on the treatment group. Throughout the study, participants undergo regular assessments including imaging such as mammograms or MRI within six months before enrollment, and clinical evaluations to monitor tumor recurrence. The main outcome measured is the time to invasive or non-invasive ipsilateral breast tumor recurrence over five years. Safety, adherence to therapy, and recovery from surgery are also monitored. The total participation period includes at least five years to evaluate long-term recurrence rates.

Researchers are investigating the effectiveness of Daromun, a neoadjuvant intratumoral treatment, combined with surgery and adjuvant therapy in patients with Stage IIIB, IIIC, and IIID melanoma. The study aims to see if this combination can significantly improve recurrence-free survival compared to the current standard care, which consists of surgery and adjuvant therapy alone. This Phase 3, open-label, randomized, controlled trial will enroll 186 patients and includes follow-up for up to six years to assess long-term outcomes. Participants will be randomly assigned to one of two groups: one group will receive Daromun injections into eligible skin, subcutaneous, or nodal tumors once weekly for up to four weeks before surgery, followed by adjuvant therapy chosen by the investigator. The other group will undergo surgery followed by adjuvant therapy without Daromun. Both groups may receive local approved post-surgery treatments such as immune checkpoint inhibitors, targeted therapies, or interferon, depending on physician discretion. During the study, participants will undergo regular assessments including clinical evaluations and laboratory tests to monitor health and treatment effects. The main outcome measured is recurrence-free survival up to 60 months after randomization. Researchers will also collect survival information for an additional year. Participants will be followed closely to track any side effects and the overall effectiveness of the treatments over time.

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 two different doses of quizartinib as maintenance therapy for adults with acute myeloid leukemia (AML) who have a specific FLT3-ITD mutation and are in their first complete remission after initial treatment. This phase 2, multicenter, randomized trial focuses on patients who have not undergone allogeneic hematopoietic stem cell transplantation. The study also includes a Holter sub-study to monitor how rapid heart rate changes might affect the heart safety of quizartinib. Participants are randomly assigned to one of two groups: one receiving a higher daily oral dose of quizartinib and the other receiving a lower daily oral dose. The maintenance treatment starts within 60 days after the last consolidation therapy cycle. The Holter sub-study involves continuous heart monitoring to evaluate cardiac effects during treatment. During the study, participants will be closely monitored for serious treatment-emergent adverse events from the first dose until 30 days after the last dose, for up to 87 months. Researchers will conduct regular assessments including physical exams, blood tests, and heart monitoring to track safety and effectiveness. The total participation duration can extend to several years to ensure long-term safety and treatment impact.