Somerville

Researchers are evaluating the effectiveness of pembrolizumab combined with sacituzumab govitecan-hziy compared to standard chemotherapy treatments in patients with advanced urothelial cancer that has spread locally or to other parts of the body. This phase III trial focuses on patients whose cancer has not responded to prior anti-PDL1 therapy. The study aims to compare overall survival, progression-free survival, response rates, duration of response, treatment side effects, and quality of life between the new combination therapy and usual chemotherapy care. Participants are randomly assigned to one of two treatment groups. One group receives standard chemotherapy options such as carboplatin or cisplatin with gemcitabine, or alternatively docetaxel or paclitaxel, given intravenously in 21-day cycles for up to six cycles or until disease progression or unacceptable side effects. The other group receives pembrolizumab intravenously on day 1 and sacituzumab govitecan-hziy intravenously on days 1 and 8 every 21 days for up to 35 cycles or two years, unless disease progresses or side effects become unacceptable. Both groups undergo blood tests and imaging scans like CT or MRI throughout the study. During the trial, participants will have regular assessments including blood sample collection and imaging to monitor their cancer status and treatment effects. Researchers will also evaluate patient-reported quality of life and fatigue at multiple time points up to 12 months. After completing treatment, participants are followed up 30 days later and then annually for five years to track survival and health outcomes. This comprehensive approach helps researchers understand both the clinical outcomes and the impact on patients well-being over time.

Researchers are studying two surgical procedures to reduce the risk of ovarian cancer in women with BRCA1 genetic mutations. This trial compares bilateral salpingectomy, which removes only the fallopian tubes, with bilateral salpingo-oophorectomy, which removes both fallopian tubes and ovaries. The goal is to find out if removing just the fallopian tubes with delayed ovary removal is nearly as effective as removing both from the start. Participants choose between two groups one undergoes bilateral salpingectomy with the option of later ovary removal, and the other undergoes bilateral salpingo-oophorectomy. Both groups have imaging tests like pelvic ultrasounds or pelvic MRIs during screening and provide blood samples throughout the study. Follow-up visits occur at multiple time points, including 10 to 60 days, 6 months, 12 months, 24 months, and then yearly for up to 20 years. During the study, researchers track if ovarian or related cancers develop and assess symptoms related to estrogen loss, quality of life, cancer-related distress, sexual function, menopausal symptoms, medical decision making, and any adverse events. Various questionnaires and imaging tests support these evaluations. Long-term safety and cancer risk reduction are monitored for up to two decades after surgery.

Researchers are evaluating the efficacy, safety, and tolerability of adding ponsegromab to systemic chemotherapy compared to chemotherapy plus placebo for adults with metastatic pancreatic ductal adenocarcinoma mPDAC who have cachexia, a condition causing significant weight loss and fatigue. This Phase 2b3 randomized, double-blind, multinational study focuses on first-line treatment for this advanced cancer and associated cachexia. Participants will receive standard first-line chemotherapy regimens, either nab-paclitaxel plus gemcitabine or FOLFIRINOX, combined with either ponsegromab at one of two doses or a matching placebo. Study intervention is given subcutaneously every four weeks starting on the same day as the chemotherapy cycle and prior to chemotherapy administration. After Phase 2b, one ponsegromab dose will be selected for Phase 3, and participants will either continue or switch to that dose while remaining blinded. An optional open-label extension allows participants to receive ponsegromab for up to 12 months after the double-blind phase. During the study, participants will have tumor assessments approximately every 6 to 8 weeks by independent radiologists. Researchers will measure changes in body weight, anorexia symptoms, physical activity, muscle and fat tissue quality, overall survival, and treatment safety through laboratory tests, adverse event monitoring, and patient questionnaires. The study duration extends through Phase 3 with ongoing monitoring until key survival events occur, with an additional optional sub-study assessing caregiver quality of life.

Researchers are evaluating whether adding the immunotherapy drug durvalumab to the usual chemotherapy regimen can improve outcomes for patients with MammaPrint High 2 Risk MP2 stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial focuses on comparing breast cancer event-free survival and other measures between patients receiving chemotherapy alone and those receiving chemotherapy with durvalumab. Immunotherapy may help enhance the bodys immune response against cancer, while chemotherapy works to stop tumor growth in various ways. Participants are first tested for MP2 status using MammaPrint on previously collected tissue. Those with MP2 results are randomized into two groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for six cycles, followed by doxorubicin and cyclophosphamide intravenously every 14 days for four cycles. The other group receives the same chemotherapy schedule combined with durvalumab given intravenously over 60 minutes on specific cycles. Mammography and optional tumor tissue and blood sample collections occur during the study. During the study, participants undergo assessments including mammography, tumor biopsies, blood tests, and quality-of-life questionnaires. Researchers measure outcomes such as event-free survival, response rates, relapse-free survival, overall survival, treatment side effects, and patient-reported fatigue and physical health. After treatment completion, participants are followed for up to 10 years to monitor long-term outcomes and survival. Specimens are also banked for future research.

Researchers are evaluating a new schedule of alternating cycles of chemoimmunotherapy chemotherapy plus pembrolizumab and immunotherapy pembrolizumab alone as the first treatment for patients with advanced lung or head and neck cancers. This phase II study aims to see if less frequent chemotherapy during the induction phase can effectively control the cancer while preserving quality of life. The trial also monitors safety and response rates over time. The study has three groups based on cancer type. Each group receives alternating cycles combination chemoimmunotherapy cycles consisting of drugs like carboplatin, paclitaxel, pemetrexed, or 5-fluorouracil with pembrolizumab, followed by cycles of pembrolizumab alone. The number of cycles varies by group, with up to four or six cycles during induction. After induction, maintenance therapy with pembrolizumab alone or combined with pemetrexed continues for up to two years. Participants will have regular assessments including imaging and laboratory tests before and during treatment to measure tumor response and monitor side effects. Researchers will track how many patients complete the induction therapy cycles and evaluate overall response rates at 6 weeks. Safety is monitored throughout the study, which can last up to three years for progression and adverse event follow-up. Patients will provide informed consent and be closely monitored during the trial.

Researchers are evaluating how to best recommend chemotherapy for patients with Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.

This research aims to evaluate the safety and effectiveness of adjusting fluoropyrimidine FP chemotherapy doses based on genetic testing for DPYD variants in cancer patients. The study focuses on patients with cancers such as colorectal, breast, head and neck, and gastrointestinal neoplasms. It compares the occurrence of severe FP-related toxicities in patients with one DPYD gene variant receiving reduced doses against patients with normal DPYD genes receiving standard doses. This prospective treatment study seeks to validate DPYD-guided dosing strategies in a real-world clinical setting. Participants receive treatment in two groups the control arm receives 100% of standard FP doses according to the BEACON order plan, with dose reductions applied if severe toxicities occur. The experimental arm includes patients with one DPYD variant who start with 50% of the regular FP dose for the first two cycles, with possible dose escalation if tolerated. The chemotherapy drugs studied include Fluorouracil injection and Xeloda Capecitabine. Throughout the study, participants are monitored for severe fluoropyrimidine-related toxicities Grade 3 to 5 over a period of up to 24 months. Researchers will also track patterns of dose modifications, such as reductions or escalations. The study involves genetic testing before therapy, regular assessments of treatment response and safety, and follow-up to measure outcomes related to toxicity and treatment adjustments.

Researchers are studying premenopausal women with early-stage breast cancer that is estrogen receptor-positive and HER2-negative, focusing on tumors with specific gene recurrence scores. The trial aims to find out if adding chemotherapy to ovarian function suppression plus endocrine therapy improves invasive breast cancer-free survival compared to ovarian function suppression plus endocrine therapy alone. This Phase III trial addresses the need for better treatments in younger women, given their higher risk and past conflicting study results on ovarian suppression and chemotherapy. Participants are randomly assigned to one of two groups one receiving ovarian function suppression combined with an aromatase inhibitor for five years, and the other receiving adjuvant chemotherapy followed by the same ovarian function suppression and aromatase inhibitor regimen. Choices for the aromatase inhibitor and gonadotropin releasing hormone agonist are made by the investigator, with options including drugs such as goserelin, leuprolide, or triptorelin. Endocrine treatment beyond five years is at the investigators discretion, and bilateral oophorectomy may be used instead of ovarian suppression if preferred. During the study, participants are monitored over 11 years from randomization, with measurements including invasive breast cancer-free survival as the primary outcome. Secondary outcomes include disease-free survival, overall survival, recurrence intervals, menopausal symptoms, and pain during aromatase inhibitor therapy. Safety and treatment effects are assessed through regular evaluations, and participants continue to be followed long term to understand the impact of treatments on their breast cancer outcomes.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase IIIII trial aims to develop a genomic screening method for large cancer populations and assign participants to appropriate sub-studies based on specific cancer biomarkers. The goal is to compare new targeted therapies designed to block cancer growth or spread with standard care, including sub-studies for patients not eligible for biomarker-driven treatments. The study involves screening patient specimens to determine eligibility for various biomarker-driven or non-matched sub-studies within the Lung-MAP umbrella protocol. This is a screening study without direct interventions instead, patients are assigned to different treatment sub-studies, each operating independently. The protocol also includes an optional ancillary study evaluating attitudes about the return of somatic mutation findings suggestive of germline mutations. Participants provide tumor tissue for biomarker testing, including molecular profiling and PD-L1 analysis, and may submit fresh biopsies and blood samples for circulating tumor DNA testing. Researchers will monitor screening success rates up to three years and collect patient and physician feedback on genetic findings. Participation involves signing informed consent, providing smoking history, and possibly completing surveys. The study duration and assessments vary depending on sub-study assignment and patient progression.

Researchers are evaluating the safety and effectiveness of melatonin to prevent antibiotic-associated acute kidney injury in hospitalized patients. This Phase 3 interventional study focuses on patients receiving broad-spectrum antibiotics, specifically vancomycin plus piperacillintazobactam, as these medications can increase the risk of kidney injury during treatment. Participants will be randomly assigned to receive either a 5 mg melatonin capsule or a matching placebo capsule by mouth at bedtime. This treatment will continue for the duration of hospitalization or until the discontinuation of the antibiotic therapy, whichever occurs first. The study is double-blinded, meaning neither participants nor researchers know which treatment is given. During the study, participants will be followed closely throughout their hospitalization or until antibiotics stop. Researchers will monitor the occurrence of acute kidney injury from the time of randomization up to 28 days or until antibiotic discontinuation. Various health assessments will be conducted to evaluate safety and treatment effects, with the primary focus on kidney function during this period.