Somerville

Researchers are evaluating the effectiveness of pembrolizumab combined with sacituzumab govitecan-hziy compared to the standard chemotherapy treatments in patients with locally advanced or metastatic urothelial cancer. This Phase III trial focuses on cancers that have spread to nearby tissues, lymph nodes, or other parts of the body. The study aims to compare overall survival and other outcomes such as progression-free survival, response rates, clinical benefits, duration of response, and treatment toxicity between the two treatment approaches. Quality of life and fatigue are also assessed as secondary measures. Participants are randomly assigned to one of two treatment groups. One group receives standard of care chemotherapy, which may include carboplatin or cisplatin combined with gemcitabine, or alternatively docetaxel or paclitaxel, administered intravenously in cycles every 21 days for up to six cycles, unless the disease progresses or side effects become unacceptable. The other group receives sacituzumab govitecan-hziy intravenously on days 1 and 8, along with pembrolizumab intravenously on day 1 of each 21-day cycle, continuing for up to 35 cycles or two years, unless there is disease progression or unacceptable toxicity. Throughout the study, participants undergo regular blood sample collections and imaging scans using computed tomography or magnetic resonance imaging to monitor their condition. Quality of life questionnaires are also completed to assess symptoms and fatigue over time. After treatment ends, patients are followed up 30 days later and then annually for up to five years to evaluate long-term outcomes and safety. The main outcome measured is overall survival from the time of randomization up to five years.

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 a new treatment schedule for patients with advanced lung or head and neck cancers. This study focuses on alternating cycles of combined chemotherapy and immunotherapy with immunotherapy alone during the initial treatment phase. The goal is to see if less frequent chemotherapy, given once every six weeks instead of every three weeks, can effectively control cancer while maintaining quality of life. This is a three-arm, parallel phase II study assessing the safety, tolerability, and effectiveness of these treatments. The study involves three treatment groups receiving different combinations of chemotherapy drugs (including Paclitaxel, Pemetrexed, 5Fluorouracil, Carboplatin) and the immunotherapy drug Pembrolizumab. Treatment during the induction phase alternates between chemoimmunotherapy and immunotherapy alone to reduce chemotherapy exposure. Patients with specific types of lung or head and neck cancers are assigned to different study arms based on cancer histology. Treatment cycles vary up to six cycles for head and neck cancer patients. Participants will undergo assessments including imaging and laboratory tests before and during treatment to evaluate tumor response and safety. Researchers will track the percentage of patients completing chemotherapy cycles, response rates at six weeks, and the best overall response. Safety and tolerability of the treatments will also be monitored throughout the study. The study requires informed consent and regular clinical evaluations to ensure participant health and study compliance.

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 the safety and effectiveness of adjusting fluoropyrimidine chemotherapy doses based on genetic testing for DPYD variants. Fluoropyrimidines like 5-Fluorouracil and Capecitabine are important treatments for cancers such as colorectal, breast, head and neck, and gastrointestinal cancers. This Phase 4 study focuses on patients with a single DPYD gene variant (heterozygotes) to compare reduced dosing guided by genetic results versus standard dosing in patients without these variants, aiming to reduce severe treatment-related toxicities. The study involves two groups: one with DPYD heterozygous variants receiving a reduced dose of fluoropyrimidines, and a control group with normal DPYD genes receiving standard dosing. Treatments include Fluorouracil injection and Xeloda (Capecitabine), with possible dose escalation to 75% or 100% if well tolerated. DPYD testing is done before starting chemotherapy to assign participants appropriately. The study includes patients receiving first-line therapy, including FOLFOX regimen, and monitors dosing adjustments based on tolerance. Participants will be assessed for the occurrence of severe fluoropyrimidine-related toxicities over 24 months. Researchers will monitor treatment effects through clinical evaluations and genetic testing results. Inclusion criteria require confirmed cancer diagnosis and DPYD testing from certified labs before treatment. The study excludes patients who cannot receive fluoropyrimidines or have multiple DPYD variants, as well as pregnant women and children. The trial aims to provide real-world validation of DPYD-guided dosing strategies to better balance safety and treatment effectiveness.

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 a screening and multi-sub-study randomized phase II/III trial called Lung-MAP, designed for patients with previously treated non-small cell lung cancer. The trial aims to establish a genomic screening method to assign patients to biomarker-driven or non-matched sub-studies. Depending on the cancer biomarker type, participants may receive new targeted cancer therapies or combinations compared to standard care, with the goal of approving new treatments. An optional ancillary study explores patient and physician attitudes about returning genetic findings related to germline mutations. The study involves testing patient specimens to determine eligibility for various sub-studies under the Lung-MAP protocol. Patients undergo screening to analyze tumor tissue and blood samples for biomarkers including PD-L1 and c-MET. Those requiring a fresh biopsy also submit blood for circulating tumor DNA testing. Sub-study assignment depends on the molecular profile results. This screening process includes both patients progressing after prior therapy and those pre-screened before progression on current treatment. Participants provide informed consent and tumor tissue that meets quality standards for testing. Researchers collect clinical data including smoking history and performance status. Outcomes focus on screening success, such as adequate tissue submission and matching to biomarker-driven sub-studies, tracked for up to three years. The study also monitors patient and physician knowledge and preferences regarding genomic findings. Participation duration varies based on screening and sub-study assignment.

Researchers are evaluating the safety and effectiveness of melatonin to prevent antibiotic-associated acute kidney injury in hospitalized patients. The study focuses on adults aged 18 to 75 years who are receiving broad-spectrum antibiotics, specifically vancomycin combined with piperacillin/tazobactam. This Phase 3 trial aims to understand if melatonin can reduce the risk of kidney damage related to these antibiotics. Participants will be randomly assigned to receive either melatonin 5 mg capsules or matching placebo capsules, taken by mouth at bedtime. The treatment will continue throughout the hospitalization or until the broad-spectrum antibiotic therapy is stopped. The study team will carefully compare outcomes between the melatonin and placebo groups. During the study, participants will be monitored for acute kidney injury from the time of randomization up to 28 days or until antibiotic discontinuation. The study team will assess safety and other outcomes while participants remain in the hospital. Monitoring will include reviewing clinical status and laboratory results to track kidney function and any adverse events.

Researchers are evaluating the effect of NBT-NM108, a high dietary fiber formula, in reducing chemotherapy-induced diarrhea in patients with metastatic colon cancer. This phase II trial focuses on patients receiving irinotecan-based chemotherapy, which commonly causes diarrhea, sometimes severe. The study aims to see if NBT-NM108 can improve gut health and function, thus reducing diarrhea symptoms and helping patients better tolerate irinotecan treatment. Participants receive irinotecan-based chemotherapy per standard care while taking NBT-NM108. The primary outcome measured is the dose intensity of irinotecan given per week. Secondary outcomes include the percentage of patients needing dose changes due to diarrhea, severity of diarrhea, tumor response, and progression-free survival. Exploratory outcomes analyze changes in gut microbiota, production of beneficial short-chain fatty acids, gut inflammation markers, and gut barrier function. During the study, researchers will monitor treatment-related side effects using standard toxicity criteria and assess tumor response by imaging before treatment and six weeks after. Participants will have lab tests and evaluations of their gut microbiome and inflammation. The study tracks how well patients tolerate chemotherapy and the impact of NBT-NM108 over the treatment period, helping understand its potential benefits and safety in this patient group.