Crown Point

Researchers are evaluating the effects of ASTX727 combined with iadademstat versus ASTX727 alone in patients with accelerated or blast phase Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including subtypes like polycythemia vera and myelofibrosis. This phase II trial aims to compare the complete acute leukemia response rate within four 28-day treatment cycles and assess survival outcomes and transplant rates. The study also explores molecular changes and resistance pathways related to these treatments. Participants are randomly assigned to one of two groups: one receives ASTX727 alone, which is a combination of decitabine and cedazuridine taken orally once daily on days 1 through 5 of each cycle; the other group receives the same ASTX727 dosing plus iadademstat taken orally on days 1-5, 8-12, 15-19, and 22-26. Treatment cycles repeat every 28 days until disease progression or unacceptable side effects occur. The study includes a dose escalation phase before randomization. During the study, participants undergo buccal swab, blood sample collections, and bone marrow aspiration and biopsy to monitor disease and treatment effects. After stopping treatment for reasons other than disease progression, patients are followed up every three months; if stopping due to progression, follow-up occurs every six months. Researchers measure treatment response using established leukemia criteria and track safety and overall survival throughout the study.

Researchers are evaluating a drug called sigvotatug vedotin alone and in combination with pembrolizumab, with or without chemotherapy, to determine its safety and effects in people with various advanced solid tumors. This Phase 1 study includes participants with specific cancers like non-small cell lung cancer, head and neck squamous cell cancer, HER2-negative breast cancer, esophageal cancers, ovarian cancer, and others. The trial aims to find out the side effects of sigvotatug vedotin and whether it can treat these solid tumors effectively. The study is divided into four parts. Part A focuses on finding the right dose of sigvotatug vedotin. Part B tests the safety and effectiveness of that dose. Parts C and D look at the safety and effectiveness of sigvotatug vedotin combined with pembrolizumab alone or with chemotherapy drugs carboplatin or cisplatin. Participants receive these drugs intravenously, with pembrolizumab given every 3 or 6 weeks and chemotherapy every 3 weeks depending on the drug. During the study, participants undergo tumor biopsies, physical exams, and disease assessments to monitor treatment effects. Researchers track side effects, lab abnormalities, and dose-limiting toxicities for up to 30-37 days after the last dose of sigvotatug vedotin, and for up to 3 years after pembrolizumab treatment. The study follows participants with regular safety monitoring and evaluations of tumor response throughout the trial.

Researchers are evaluating two surgical procedures, bilateral salpingectomy and bilateral salpingo-oophorectomy, to see how well they reduce the risk of ovarian cancer in women who have BRCA1 gene mutations. The study aims to determine if removing just the fallopian tubes (bilateral salpingectomy) is almost as effective as removing both the fallopian tubes and ovaries (bilateral salpingo-oophorectomy) in lowering ovarian cancer risk. This trial also assesses symptoms related to estrogen loss, quality of life, sexual function, cancer-related distress, decision-making about surgery, and treatment side effects in these patients. Participants choose between two groups: one group undergoes bilateral salpingectomy and may have their ovaries removed later, while the other group undergoes bilateral salpingo-oophorectomy. Both groups receive pelvic or transvaginal ultrasounds or pelvic MRI scans during screening, and blood samples are collected throughout the trial. Ancillary studies include quality-of-life assessments and questionnaires. The study also collects tissue and blood samples for future research. After surgery, participants have follow-up visits at 10 to 60 days, then at 6, 12, and 24 months, and annually for up to 20 years. Researchers monitor the time until any high-grade serous carcinomas develop, specifically ovarian, primary peritoneal, or fallopian tube cancers. They also track menopausal symptoms, sexual function, quality of life, cancer distress, medical decisions about surgery, and any adverse events during this long-term follow-up.

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 the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab in patients with advanced or locally unresectable stomach or esophageal adenocarcinoma. This phase II/III trial aims to determine if adding nivolumab improves progression-free survival and overall survival compared to paclitaxel and ramucirumab alone. The study also assesses response rates, disease control, safety, tolerability, and quality of life in participants with PD-L1 CPS 21 1 advanced gastric or esophageal cancer. Participants are randomly assigned to one of two treatment groups. The first group receives nivolumab IV on day 1 of each 28-day cycle, ramucirumab IV on days 1 and 15, and paclitaxel IV on days 1, 8, and 15. The second group receives ramucirumab IV on days 1 and 15 and paclitaxel IV on days 1, 8, and 15 of each cycle. Treatment continues every 28 days until disease progression or unacceptable side effects occur. Optional blood samples may be collected during the study. Imaging with CT and MRI is performed throughout. Participants undergo scans and assessments at baseline and during treatment to monitor cancer progression and treatment effects. They also complete questionnaires on quality of life and symptoms. After treatment ends, participants are followed up at 30, 60, and 90 days and then every 6 months for up to 3 years. Researchers measure progression-free survival and overall survival as primary outcomes, along with other safety and patient-reported measures.

Researchers are evaluating the addition of olaparib, a PARP inhibitor, as maintenance therapy following surgery and chemotherapy in patients with pancreatic cancer that has been surgically removed and who have a pathogenic mutation in BRCA1, BRCA2, or PALB2 genes. This phase II randomized, double-blind study aims to determine if olaparib can improve relapse-free survival compared to placebo in these patients, who have completed perioperative chemotherapy and have no evidence of recurrent disease. Participants are randomly assigned to receive either olaparib or a placebo orally twice daily in 28-day cycles for up to 12 cycles, as long as there is no disease progression or unacceptable side effects. Throughout the treatment period, patients undergo imaging tests such as CT scans or MRI and blood sample collections. After completing the treatment cycles, patients are followed up at 30 days, every 4 months for the first year, and then every 6 months for up to 10 years after randomization to monitor their health and disease status. During the study, researchers assess relapse-free survival by documenting any return of cancer or death from 22 to 44 months after randomization. They also collect blood samples and perform imaging tests to monitor the disease and evaluate treatment effects. Safety is carefully monitored, and patients must have recovered from previous treatments before starting the study. The study includes long-term follow-up to observe survival outcomes and any differences based on genetic mutations or prior chemotherapy regimens.

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 evaluating three different combinations of drugs to treat newly diagnosed multiple myeloma in patients who are considered frail or intermediate-fit and are not eligible for stem cell transplant. This phase III trial focuses on comparing these three-drug induction treatments followed by either double- or single-drug maintenance therapy. The study aims to determine which treatment combination better controls the disease and improves progression-free survival and overall survival. Patients are randomly assigned to one of three treatment groups. Arm 1 (VRd-Lite) receives bortezomib by injection under the skin, lenalidomide by mouth, and dexamethasone by mouth during induction cycles, followed by lenalidomide alone for maintenance. Arm 2 (DRd-R) receives daratumumab and hyaluronidase-fihj injections, lenalidomide, and dexamethasone during induction, followed by lenalidomide alone during maintenance. Arm 3 (DRd-DR) receives the same induction as Arm 2, but maintenance includes both daratumumab and lenalidomide. Induction cycles last up to 9 cycles of 28 days each, and maintenance cycles continue every 28 days if the disease does not progress or toxicity occurs. Participants undergo assessments including tumor evaluations, whole-body imaging, blood tests, and quality-of-life questionnaires. After completing treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years. Researchers will measure progression-free survival, overall survival, response rates, safety, minimal residual disease, and patient-reported health outcomes to understand the treatments' effects and support future care decisions.

Researchers are evaluating different treatment combinations for younger patients with intermediate risk acute myeloid leukemia (AML) in this phase II MyeloMATCH trial. The study compares three regimens: cytarabine with daunorubicin, cytarabine with daunorubicin plus venetoclax, and venetoclax with azacitidine. The goal is to see if adding venetoclax improves the elimination of AML cells by at least 20% compared to the standard cytarabine and daunorubicin treatment. Participants are randomly assigned to one of three treatment groups. One group receives daunorubicin intravenously on days 2-4, continuous intravenous cytarabine on days 2-8, and oral venetoclax daily on days 1-11, with possible reinduction cycles. Another group receives azacitidine intravenously or subcutaneously on days 1-7 or days 1-5 and 8-9, plus oral venetoclax daily for 28 days, repeated for 2 cycles. The last group receives daunorubicin intravenously on days 1-3 and continuous intravenous cytarabine on days 1-7, with possible reinduction. Treatments continue unless disease progresses or unacceptable side effects occur. During the study, participants undergo bone marrow aspirations and blood sample collections to monitor response. Follow-up visits occur 4 weeks after treatment, then every 3 months for the first year, every 6 months in the second year, and yearly afterward. Researchers measure how well the treatments eliminate measurable residual disease and assess remission rates, side effects, survival outcomes, and treatment responses based on genetic features.