Scarborough

Researchers are evaluating zanidatamab combined with chemotherapy to treat people with early-stage HER2-positive breast cancer. This Phase 2 study focuses on patients with Stage II or III invasive breast carcinoma that is confirmed to be HER2-positive. The purpose is to assess the safety and effectiveness of this combination treatment before surgery. Participants receive zanidatamab and chemotherapy drugs such as paclitaxel, docetaxel, carboplatin, trastuzumab, and pertuzumab, all administered intravenously. After completing neoadjuvant therapy, participants agree to undergo either a mastectomy or breast-conserving surgery. The study is open-label and conducted at multiple centers. During the study, researchers monitor the participants' response by measuring the number who achieve a pathological complete response within 8 months. They also ensure participants have adequate organ function, track heart function with imaging, and evaluate treatment safety. Participants are regularly assessed to support study goals and monitor any side effects.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are investigating the best way to combine chemotherapy and radiation therapy based on how patients with localized non-germinomatous germ cell tumors (NGGCT) in the brain respond to initial chemotherapy. This phase II study aims to optimize radiation treatment for those who respond well to induction chemotherapy to reduce spinal cord relapses, and to use higher dose chemotherapy followed by conventional radiation for patients who do not respond as well. The study evaluates various chemotherapy drugs that work to stop tumor growth in different ways and uses radiation therapy with high-energy x-rays or protons to kill tumor cells and shrink tumors. Participants receive induction chemotherapy with drugs including carboplatin, etoposide, ifosfamide, and thiotepa over multiple cycles. Based on their response, patients are assigned to one of two treatment plans: those with a good response receive whole ventricular plus spinal canal irradiation (WVSCI) radiation therapy, while those with less favorable responses may receive high-dose chemotherapy with peripheral blood stem cell transplantation followed by radiation therapy. Some patients may also undergo second-look surgery depending on their tumor response. Treatments are carefully scheduled and monitored for up to six weeks for radiation and multiple cycles for chemotherapy. During the study, participants undergo regular assessments including MRI scans, cerebrospinal fluid and blood sample collections, and neurocognitive and quality of life evaluations. Researchers monitor tumor response, progression-free survival, overall survival, and treatment side effects for up to 10 years after treatment. Additional evaluations compare outcomes based on radiation type and assess growth and blood counts in younger patients. Patient safety and treatment effectiveness are closely followed throughout the study period.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are evaluating combination chemotherapy treatments for patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) and relapsed favorable histology Wilms tumors (FHWT). This phase II trial aims to assess how adding vincristine and irinotecan to standard chemotherapy regimens affects event-free survival and overall survival compared to historical data. The study also explores kidney toxicity, tumor genetics, and radiation therapy techniques to reduce side effects in children with lung and liver metastases. Two chemotherapy regimens are studied. Arm I (Regimen UH-3) involves cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan given intravenously on specific days every 21 days. Radiation therapy is given around week 7 of cycle 3 if needed. Arm II (Regimen ICE/Cyclo/Topo) includes cycles of ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan given intravenously every 21 days, with surgery and/or radiation during certain cycles. Both arms include multiple cycles in absence of disease progression or unacceptable side effects. Participants undergo various scans like CT, PET, MRI, chest x-rays, ultrasounds, and bone scans throughout the trial. Blood samples and biopsies may be collected periodically. After treatment, patients are followed up every 3 months for the first 2 years, every 6 months for years 3-4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years, along with monitoring kidney health and treatment effects.

Researchers are evaluating repotrectinib, an oral drug, in pediatric and young adult patients with advanced or metastatic cancers that have specific genetic changes involving ALK, ROS1, or NTRK1-3 genes. The study includes two phases: Phase 1 aims to find the safe dose for children under 12 years old and Phase 2 assesses the drug's anti-tumor effects in patients aged 12 to 25 years with these genetic alterations. The study focuses on cancers like solid tumors, lymphoma, and primary CNS tumors that have progressed despite other treatments or have no standard cure options. In Phase 1, approximately 12 pediatric patients under 12 receive repotrectinib to determine the recommended dose for further study. Phase 2 includes three groups: patients with NTRK fusion solid tumors who haven't had TRK inhibitor treatment; those previously treated with TRK inhibitors; and patients with ROS1 or other related gene alterations. Phase 2 involves up to 53 patients, some with measurable disease confirmed by central review. Participants take oral repotrectinib, and dosing and enrollment depend on age and genetic tumor profiles. Participants will be monitored closely with assessments to track safety, side effects, and tumor responses. Phase 1 evaluates dose-limiting toxicities within 28 days of the first dose and determines the recommended dose within 28 days after dose escalation. Phase 2 measures overall tumor response over two to three years after starting treatment. The study also monitors laboratory tests, performance status, neurological stability for CNS tumors, and life expectancy. Total participation time varies by phase and treatment response.

Researchers are evaluating the effectiveness and safety of targeted treatments with or without the immune therapy drug atezolizumab in women with recurrent or persistent endometrial cancer. This Phase IB/II multi-cohort study uses genomic screening to assign participants to groups based on their tumor's specific genetic profile, aiming to match them with targeted therapies. The study allows for new treatment groups to be added over time with committee approval. Participants receive treatments depending on their assigned group. Those in the AFT-50A Protocol receive combinations of atezolizumab with targeted drugs such as talazoparib, while the AFT-50B Protocol includes combinations of targeted agents like inavolisib with letrozole or giredestrant with abemaciclib. Treatments are given in cycles, mostly every 21 or 28 days, with drug delivery methods including intravenous infusions and oral tablets. Some treatment groups have closed to enrollment, while others are open and each group has a planned number of participants. During the study, participants undergo tumor biomarker testing before assignment and regular assessments to monitor treatment response and safety. Researchers measure the overall response rate and track how many participants survive without disease progression at six months. Close monitoring includes imaging and clinical evaluations over a period extending up to 48 months. This comprehensive approach helps to understand how these targeted and immune therapies work in this patient group.

Researchers are evaluating the safety, side effects, and best dose of selinexor combined with standard radiation therapy in children and young adults newly diagnosed with diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) that has a specific genetic mutation called H3 K27M. DIPG is a type of aggressive brain tumor that affects critical brainstem functions, while HGG refers to fast-growing brain or spine cancers. This phase I/II trial aims to find the maximum tolerated dose of selinexor and then assess how well this dose works to shrink tumors and improve survival compared to historical data. Participants receive standard radiation therapy five days a week for 5 to 7 weeks. Starting on day 4 or 5 of radiation, selinexor is given orally at specific weekly intervals during treatment. After a two-week break, patients enter a maintenance phase where selinexor is taken orally on certain days of each 28-day cycle, for up to 24 cycles if the disease does not progress or side effects are unacceptable. Some patients may undergo a biopsy and all have magnetic resonance imaging (MRI) scans during screening, treatment, and follow-up. During the study, participants are closely monitored with regular MRI scans, laboratory tests, and clinical evaluations to track tumor response and side effects. Researchers measure outcomes such as the maximum tolerated dose, event-free survival, overall survival, and overall response rate for up to five years. After treatment ends, patients are followed every 3 months for the first year, every 6 months for years 2 and 3, and yearly for years 4 and 5 to monitor long-term safety and effectiveness.

Researchers are evaluating the effects of selumetinib compared to the standard treatment with carboplatin and vincristine (CV) in patients aged 2 to 21 years with newly diagnosed or previously untreated low-grade glioma (LGG) that lacks the BRAFV600E mutation and is not linked to systemic neurofibromatosis type 1 (NF1). This phase III study aims to determine if selumetinib is as effective as the current standard treatment and to assess which treatment is better, including its impact on patients' quality of life. The trial also explores tumor response rates, visual and motor function outcomes, and cognitive and social functioning in children with LGG. Participants are randomly assigned to one of two treatment groups. In the first group, patients receive intravenous vincristine and carboplatin in an induction phase with specific dosing days, followed by a maintenance phase with repeated cycles every 42 days for up to eight cycles, unless disease progression or unacceptable toxicity occurs. In the second group, patients take oral selumetinib twice daily in 28-day cycles for up to 27 cycles, also until progression or unacceptable toxicity. Throughout the trial, patients undergo blood sample collection, magnetic resonance imaging (MRI), and in the selumetinib group, echocardiography (ECHO) at baseline. Participants are monitored during treatment and followed after completion every 3 months for the first year, every 6 months for years two and three, and then annually up to 10 years. The study measures event-free survival (EFS) as the primary outcome over this period. Additional assessments include visual acuity tests, motor function evaluations, quality of life questionnaires, cognitive and emotional function assessments, and collection of biological samples for future studies. Safety is monitored continuously to track any treatment-related effects or complications.

Researchers are evaluating the combination of blinatumomab with dasatinib or imatinib alongside standard chemotherapy to treat patients with Philadelphia chromosome-positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL). This phase 2 trial focuses on children, adolescents, and young adults under 25 years with newly diagnosed Ph+ or ABL-class Ph-like B-ALL, aiming to estimate three-year event-free survival (EFS) and assess safety and toxicity of this chemo-immunotherapy approach. Treatment involves a modified Berlin-Frankfurt-Mfcnster chemotherapy backbone with three cycles of blinatumomab replacing traditional consolidation chemotherapy. Patients with Ph+ B-ALL receive continuous dasatinib, while those with ABL-class Ph-like B-ALL receive continuous imatinib or dasatinib depending on specific gene fusions. The study includes multiple treatment phases: induction, blinatumomab blocks, interim maintenance, delayed intensification, and maintenance cycles repeated every 12 weeks for two years, with some patients possibly receiving radiation therapy. Participants undergo blood and cerebrospinal fluid sample collections, bone marrow biopsies, echocardiography or multigated acquisition scans, and various laboratory tests throughout the study. Researchers measure outcomes such as three-year event-free survival, incidence of adverse events, minimal residual disease negativity, treatment response, and overall survival. Safety monitoring includes assessments of infections, neurotoxicity, and therapy-related mortality. The total participation extends up to three years with ongoing evaluations to track treatment effects and side effects.