Scarborough

Researchers are evaluating new treatments for advanced ovarian cancer in women who have completed initial surgery and chemotherapy. The study focuses on non-HRD positive ovarian cancer, comparing a targeted therapy called sacituzumab tirumotecan sac-TMT given alone or with bevacizumab, against standard care options such as bevacizumab maintenance or observation. The goal is to see if sac-TMT with or without bevacizumab can help patients live longer without their cancer worsening. Participants in the experimental group will receive sac-TMT through intravenous infusion on days 1, 15, and 29 of every 6-week cycle until the cancer progresses, side effects become prohibitive, or other reasons for stopping arise. They may optionally receive bevacizumab on days 1 and 22 of each cycle. The comparator group will either receive bevacizumab alone every 3 weeks for up to 22 courses or be monitored without active treatment. Supportive medications like steroid mouthwash and other rescue drugs are recommended before sac-TMT infusions. Throughout the study, participants will be regularly monitored for how long they live without their disease progressing, overall survival, side effects, and quality of life using specialized questionnaires. These assessments will continue for up to approximately 78 months. The study is randomized, with single masking, and led by Merck Sharp & Dohme LLC. Participants can expect regular visits for treatment and monitoring during this period.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are evaluating zanidatamab combined with chemotherapy for treating people with HER2-positive, early-stage breast cancer. This phase 2 study aims to assess the safety and effectiveness of this combination compared to standard treatments in participants with newly diagnosed stage II or III invasive breast carcinoma. Participants are randomly assigned to one of three treatment groups zanidatamab with paclitaxel, zanidatamab with docetaxel and carboplatin, or trastuzumab and pertuzumab with docetaxel and carboplatin. All study drugs are administered intravenously. After neoadjuvant therapy, participants will undergo either mastectomy or breast conserving surgery as decided by their physician. During the study, participants will have their response to treatment assessed through measurements such as pathologic complete response and residual cancer burden classification up to 8 months. Safety is monitored by tracking treatment-related adverse events up to 23 months. Other assessments include survival outcomes up to 46 months and serum concentrations of zanidatamab. The study participation may last several years to capture these outcomes.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are comparing two chemotherapy treatment plans for patients with newly diagnosed intermediate-risk rhabdomyosarcoma, a type of soft tissue cancer. This phase III trial evaluates whether a higher dose chemotherapy over a shorter time Regimen A is better than a lower dose chemotherapy followed by maintenance treatment over a longer time Regimen B, both combined with standard surgery and radiation. The study also aims to assess survival rates, treatment side effects, and molecular features of the tumor. Participants are randomly assigned to one of two treatment groups. Regimen A involves multiple cycles of vincristine, dactinomycin, and cyclophosphamide given intravenously every 21 days, with possible surgery during week 12 and radiation treatments during specified cycles. Regimen B includes alternating cycles of vincristine, dactinomycin, cyclophosphamide, and irinotecan, followed by 24 weeks of maintenance chemotherapy with vinorelbine and oral cyclophosphamide. Both groups undergo imaging scans and biopsies as needed during treatment. Throughout the study, participants will have regular CT or MRI scans and blood tests, along with other procedures such as lymph node biopsies, bone marrow tests, and lumbar punctures to monitor disease status. After treatment, follow-up visits occur every 3 months for the first year, then less frequently up to 5 years to check for event-free survival and overall health. The trial also collects biospecimens for future research and evaluates treatment effects on fertility and quality of life.

Researchers are investigating the best way to combine chemotherapy and radiation therapy for patients aged 3 to 29 years with localized non-germinomatous germ cell tumors NGGCT in the brain. This phase II trial aims to optimize treatment based on how well the tumor responds to initial chemotherapy, with the goal of reducing spinal cord relapses and adjusting therapy for better disease control. The study also compares different radiation types and examines cognitive and physical effects in children and young adults with NGGCT. Participants first receive induction chemotherapy consisting of carboplatin, etoposide, and ifosfamide over six cycles every 21 days. Based on tumor response, patients are assigned to one of two plans Plan A involves whole ventricular plus spinal canal irradiation WVSCI, delivered daily for 6 weeks, while Plan B includes high-dose chemotherapy with stem cell transplant followed by radiation therapy to the whole brain and spine. Some patients may undergo second-look surgery depending on tumor response before continuing treatment. Throughout the study, participants undergo MRI scans, collection of cerebrospinal fluid and blood samples, and questionnaires assessing cognitive, social, and behavioral functioning. Researchers monitor tumor response, progression-free survival, overall survival, and patterns of disease recurrence for up to 10 years. Safety and side effects are also evaluated to better understand long-term outcomes of these treatment approaches.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating how well combination chemotherapy works in treating patients with newly diagnosed stages 2 to 4 diffuse anaplastic Wilms tumor DAWT and patients with relapsed favorable histology Wilms tumor FHWT. This phase II trial compares the effects of two chemotherapy regimens, UH-3 and ICECycloTopo, on event-free survival and overall survival, aiming to improve outcomes based on different relapse risk groups and prior treatments. The study also explores kidney toxicity, genetic markers, surgery impacts, and radiation therapy techniques to reduce side effects and better understand tumor behavior. Participants are assigned to one of two treatment groups. In Arm I Regimen UH-3, patients receive cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan intravenously over various days in a 21-day cycle, with radiation therapy at week 7 of cycle 3 if needed. In Arm II Regimen ICECycloTopo, patients receive cycles of carboplatin, etoposide, ifosfamide, cyclophosphamide, and topotecan intravenously over 10 cycles every 21 days, with surgery andor radiation therapy during certain cycles as clinically indicated. Throughout the trial, patients undergo multiple imaging tests including CT scans, PET scans, chest x-rays, MRIs, abdominal ultrasounds, and bone scans, along with blood sample collections and biopsies. After completing treatment, follow-up visits occur every 3 months for the first 2 years, then every 6 months for years 3 and 4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years from study entry, with ongoing monitoring for treatment effects and safety.

Researchers are evaluating a phase II trial studying how well lower dose radiotherapy after chemotherapy works in treating children and young adults with central nervous system CNS germinomas. This trial aims to compare reduced radiation doses to standard treatment while maintaining effectiveness, potentially reducing long-term side effects. The study also investigates survival rates, tumor response, neuroendocrine function, and cognitive processing speed in participants with localized, metastatic, and basal ganglia or thalamic germinomas. Participants receive chemotherapy with carboplatin and etoposide intravenously over several days, repeated every 21 days for up to four cycles. After chemotherapy, patients are assigned to different treatment groups strata based on tumor response and location. Radiation therapy is delivered using advanced techniques such as 3D conformal radiation, proton therapy, or intensity-modulated radiation daily on weekdays for 16 to 24 days depending on the stratum. Some patients may undergo second-look surgery. The study includes collection of blood, cerebrospinal fluid, and tumor tissue samples for research. Throughout the study, participants undergo MRI scans and may have lumbar punctures for cerebrospinal fluid collection. Follow-up occurs every three months for the first year, then every four months for two years, and annually up to ten years. Researchers measure event-free survival, overall survival, tumor response, neuroendocrine function, and cognitive processing speed at multiple time points. The study also monitors for cerebral vascular events and evaluates long-term cognitive, social, and behavioral outcomes.

Researchers are evaluating repotrectinib, an oral drug, in pediatric and young adult patients with advanced or metastatic cancers that have specific genetic changes in ALK, ROS1, or NTRK1-3 genes. The study includes two phases Phase 1 focuses on finding safe dose levels and the recommended dose for children under 12, while Phase 2 assesses the drugs anti-tumor activity in patients aged 12 to 25 with certain gene fusions or alterations. This study aims to address cancers that have progressed despite other treatments or have no standard cure options. In Phase 1, about 12 children under 12 years old with advanced solid tumors or lymphoma will receive different doses of repotrectinib to determine safety and the best dosing. Phase 2 includes three groups of patients aged 12 to 25, with varying genetic profiles and prior treatment histories, all receiving oral repotrectinib. The drug will be given continuously in cycles, with careful monitoring. Enrollment for Phase 1 and Phase 2 occurs simultaneously, allowing younger children to join Phase 2 once their dose is established. Participants will undergo regular assessments including scans and tests to measure tumor response, drug levels in the blood, and side effects. The study tracks several outcomes such as response rate, duration of response, survival, and brain tumor progression over approximately three years. Safety and tolerability are closely monitored during the first 28 days of treatment, with ongoing follow-up visits throughout the study period. This long-term observation helps researchers understand both the drugs effects and patient well-being.