Milford

Researchers are evaluating how well elacestrant works compared to standard endocrine therapy in adults with node-positive, Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor-2 negative (HER2-) early breast cancer who are at high risk of the cancer returning. This is a Phase 3 global, multicenter, randomized, open-label study focusing on participants who have had early invasive breast cancer removed and meet specific receptor and risk criteria. The study aims to understand which treatment better prevents invasive breast cancer over up to five years. Participants will receive either elacestrant or one of several standard endocrine therapies, including anastrozole, letrozole, exemestane, or tamoxifen, all given as oral tablets. Treatments will be administered according to the study plan, with careful monitoring throughout the trial. The study includes adults who have already received between 24 and 60 months of prior endocrine therapy, with or without certain inhibitors, and who have completed or stopped these treatments as required. During the study, participants will be monitored for invasive breast cancer-free survival for up to five years. Researchers will perform regular assessments to track treatment effects, side effects, and cancer recurrence. The study also includes safety monitoring and may involve additional tests or evaluations as needed to ensure participant well-being throughout the trial.

Researchers are evaluating the effectiveness and safety of adding Tersolisib (LY4064809/STX-478) to other anti-cancer drugs as the first treatment for adults with advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This phase 3 study focuses on participants whose cancer has a specific genetic change called a PIK3CA mutation and who have not received prior treatment for advanced breast cancer. The study aims to understand how well this treatment combination works and its safety over time. Participants will receive Tersolisib or a placebo, combined with a CDK4/6 inhibitor (Ribociclib, Palbociclib, or Abemaciclib) and endocrine therapy (Anastrozole, Letrozole, Exemestane, or Fulvestrant). All drugs are given orally except for Fulvestrant, which is given by injection into the muscle. The study includes two parts: Part 1 allows participants who have had up to two prior treatments for advanced breast cancer, including chemotherapy; Part 2 includes those with no prior treatment for advanced disease and classifies them as endocrine sensitive or resistant based on their cancer history. During the study, participants will be regularly assessed for cancer response, progression-free survival, and side effects. Researchers will monitor measurable disease or bone involvement and track overall response rates, including complete or partial tumor shrinkage. The study will continue as long as the treatment is helping without causing unbearable side effects. Follow-up may last up to five years to observe long-term outcomes and safety.

Researchers are evaluating the safety, effectiveness, and drug levels of Deucravacitinib (BMS-986165) in adolescents aged 12 to less than 18 years with moderate to severe plaque psoriasis. This phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to better understand how this treatment affects this condition in younger patients. Participants must have had stable plaque psoriasis for at least six months and meet specific severity criteria. Participants will receive either Deucravacitinib or a placebo at specified doses on designated days. The study compares the drug to placebo to assess its impact on psoriasis symptoms. No additional details about dosing schedules are provided, but the intervention period includes monitoring drug levels and safety. This design allows researchers to evaluate the treatment in a controlled and blinded manner. Throughout the study, participants will be monitored for improvement in their psoriasis using measures like the Psoriasis Area and Severity Index (PASI) and the static Physicians Global Assessment (sPGA) at week 16. Safety will also be assessed. The primary outcomes include the number of participants achieving at least 75% improvement in PASI and those reaching clear or almost clear skin with a significant reduction in sPGA score. Participants are observed from screening through the intervention period with regular assessments to track efficacy and safety.

Researchers are evaluating the safety and effectiveness of the drugs abemaciclib and letrozole in people with advanced or recurrent estrogen receptor positive (ER+), mismatch repair proficient, TP53 wild-type endometrial cancer. This phase 2, single-arm trial focuses on maintenance therapy after participants have received chemotherapy with carboplatin and paclitaxel, with or without anti-PD-(L)1 immunotherapy. Abemaciclib and letrozole are approved for other uses but not yet for endometrial cancer. The study aims to assess progression-free survival over up to 2 years. Participants will receive oral tablets of abemaciclib, a cyclin-dependent kinase (CDK) inhibitor, and letrozole, an aromatase inhibitor, as maintenance treatment for up to 2 years. Some participants may have also received pembrolizumab, an intravenous anti-PD-(L)1 antibody, during prior treatment. The study includes screening, treatment visits, and various imaging scans such as X-rays, CT, MRI, and PET scans to monitor response. Participants will have blood tests, electrocardiograms (EKGs), and other assessments throughout treatment and will be followed for 3 years after completing the study drugs. Researchers will measure progression-free survival and monitor safety. About 32 people are expected to participate. The study is supported by Eli Lilly, who provides funding and the study drug abemaciclib.

Researchers are investigating treatments for people with newly diagnosed Stage I HER2-positive invasive breast cancer. This phase II study compares two different combinations of HER2-targeted therapies after surgery to evaluate their effects and side effects. The study focuses on whether trastuzumab-emtansine (T-DM1) followed by subcutaneous trastuzumab has fewer side effects than the standard treatment of paclitaxel combined with subcutaneous trastuzumab, while also looking at long-term benefits and disease-free survival. Participants will be randomly assigned to one of two groups. One group will receive trastuzumab-emtansine (T-DM1) through intravenous infusion followed by subcutaneous trastuzumab injections. The other group will receive paclitaxel through intravenous infusion combined with subcutaneous trastuzumab injections. Treatments will be given for a total of one year. T-DM1 is a targeted therapy that combines an antibody with chemotherapy to directly attack cancer cells. During the study, participants will undergo screening, laboratory tests, and regular follow-up visits over five years after treatment ends. Researchers will monitor side effects during the first 18 weeks of treatment and measure disease-free survival up to 72 months. The study includes assessments of heart function, blood tests, and collection of tumor tissue for research. About 500 people are expected to participate.

Researchers are evaluating the effect of adding chemotherapy to immunotherapy (pembrolizumab) compared to using immunotherapy alone in treating older adults aged 70 and above with advanced non-small cell lung cancer (stage IIIB-IV). This phase III trial aims to determine if combining chemotherapy with pembrolizumab improves overall survival and other outcomes like progression-free survival, response rates, toxicity, and quality of life in this vulnerable patient group. Participants are randomly assigned to one of two treatment groups. In the immunotherapy-alone group, patients receive pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years if there is no disease progression or unacceptable side effects. In the combination group, patients receive pembrolizumab plus a chemotherapy regimen chosen by their doctor, including drugs such as pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel, given intravenously on specific schedules for four cycles, followed by the same pembrolizumab maintenance. Imaging scans like MRI, CT, and PET are performed at baseline and throughout the study. During the study, participants undergo various assessments including imaging scans, laboratory tests, and questionnaires to evaluate treatment effects, side effects, and quality of life. Researchers monitor overall survival for up to five years from randomization, with follow-up visits every three months for the first two years and every six months thereafter until five years. Additional exploratory analyses include safety, tolerability, and correlations with gut microbiome and geriatric assessments to better understand treatment outcomes in this population.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer after surgery by using the presence or absence of circulating tumor DNA (ctDNA) in the blood. This approach aims to identify microscopic residual tumor cells and may provide better risk prediction for cancer recurrence compared to traditional methods. The trial focuses on patients with Stage IIB, IIC, or III colon cancer who have undergone complete tumor removal. Participants will have their tumor tissue and blood tested centrally using the Signatera assay to determine ctDNA status. Patients without detectable ctDNA may avoid chemotherapy, while those with detectable ctDNA are considered at higher risk and will be randomly assigned to receive different chemotherapy regimens, including mFOLFOX6, CAPOX, or mFOLFIRINOX, given intravenously or orally over periods ranging from 3 to 6 months. The study includes initial screening, treatment, and possible second randomization for patients whose ctDNA status changes during monitoring. During the study, participants will undergo various assessments including blood tests, imaging scans, and performance evaluations to monitor their health and response to therapy. Researchers will track the time to ctDNA positivity and disease-free survival for up to 3 and 5 years, respectively. Safety and treatment effects will be closely observed throughout the study duration, ensuring thorough follow-up and monitoring for all participants.

Researchers are conducting a multicenter, randomized, double-blinded, placebo-controlled study to find the best dose of ORKA-002 for adults with moderate-to-severe plaque psoriasis. The study aims to evaluate the effectiveness and safety of ORKA-002 compared to a placebo. Approximately 160 adult participants diagnosed with plaque psoriasis for more than 6 months, who are candidates for systemic therapy or phototherapy, will take part in this Phase 2 trial. Participants will receive one of three induction dosing regimens of ORKA-002 or a placebo, both administered by subcutaneous injection. The study consists of three periods: a screening period, an induction period where treatment is given, and a post-treatment follow-up period to monitor outcomes and safety. The goal is to identify the optimal dosing regimen that provides the best balance of efficacy and safety. During the study, participants will be assessed for the proportion achieving complete clearance of psoriasis skin symptoms (100% reduction in PASI score) by week 16. Researchers will also monitor for any treatment-emergent adverse events or serious side effects through week 48. Participants will undergo various evaluations including clinical assessments and safety monitoring throughout the study duration.

Glioblastoma (GBM) is a fast-growing cancer of the central nervous system that affects older adults who have unique medical and care needs. Researchers are investigating whether increasing the daily dose of radiation therapy over a shorter time, called dose-escalated hypofractionated radiation, can improve outcomes compared to the standard radiation treatment in older adults with newly diagnosed GBM. This is a Phase 2 hybrid randomized trial comparing these two radiation approaches in this population. Participants will receive radiation therapy over a three-week period. One group will get the standard hypofractionated radiation treatment, while the other group will receive a higher daily dose of radiation, known as dose-escalated radiation therapy, during the same three weeks. Treatment will be carefully planned and delivered to target the tumor while monitoring safety and effectiveness. During the study, participants will undergo screening to confirm eligibility, attend clinical visits for radiation treatment, and have regular assessments to monitor symptoms and treatment effects. Researchers will track overall survival from enrollment through about one year of follow-up. Throughout the trial, symptom evaluations and safety checks will be done at scheduled times to ensure participant well-being and to gather important data on treatment impact.

Researchers are evaluating AZD9592 in a first-in-human Phase I study involving patients with advanced solid tumors, including non-small cell lung cancer, head and neck cancers, and colorectal cancer. The study aims to assess the safety, tolerability, preliminary effectiveness, pharmacokinetics, pharmacodynamics, anti-tumor activity, and immune response to AZD9592 alone or combined with other anti-cancer drugs. Participants will receive varying doses of AZD9592 either as monotherapy or together with other cancer treatments such as oral Osimertinib tablets or intravenous infusions of 5-Fluorouracil, Leucovorin, and Bevacizumab. The study includes different modules focusing on specific cancer types and treatment combinations. This open-label, multi-center trial involves dose escalation and expansion phases to evaluate treatment effects. During the study, participants will be closely monitored for adverse events, serious side effects, dose-limiting toxicities, changes in laboratory tests, ECG, and vital signs from consent until 30 days after the last AZD9592 dose. Researchers will also measure tumor response through imaging up to about two years or until disease progression. Overall, the study involves detailed safety and response assessments to understand the impact of AZD9592 in these cancers.