Auburn

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

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 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 a phase II Lung-MAP treatment trial testing combinations of targeted drugs—capmatinib, osimertinib, and ramucirumab—to treat patients with advanced non-small cell lung cancer (NSCLC) that has spread and shows EGFR and MET gene changes. Capmatinib and osimertinib are kinase inhibitors that block abnormal proteins signaling cancer growth, while ramucirumab is an antibody that may stop new blood vessel growth needed by tumors. Targeting these gene changes may help shrink or control the cancer. Patients are randomized into two groups: one group receives capmatinib and osimertinib orally along with ramucirumab intravenously, while the other group receives capmatinib and osimertinib orally without ramucirumab. Throughout the study, participants undergo CT or MRI scans and provide blood samples. The treatments are given according to the assigned group to compare their effects and safety. During the trial, participants are closely monitored with imaging and blood tests to assess cancer progression and treatment side effects. The main measure is progression-free survival, tracking time until cancer worsens or death, over up to 3 years. Researchers also evaluate response rates, overall survival, toxicity, and collect tissue and blood samples to study tumor DNA. Participants' health status and laboratory values are regularly checked to ensure safety and effectiveness of the treatments.

Researchers are evaluating treatments for patients with metastatic kidney cancer to see if adding surgery to standard immunotherapy-based drug combinations improves outcomes. This phase III trial focuses on kidney cancer that has spread to other parts of the body. The study compares standard immunotherapy drugs, which help the immune system fight cancer, with or without the surgical removal of the kidney, known as nephrectomy. Doctors currently do not agree on whether surgery adds benefit when combined with these immunotherapy treatments. Participants first receive one of three immunotherapy-based drug regimens, including combinations of nivolumab, ipilimumab, pembrolizumab, avelumab, and axitinib, given through intravenous infusions and oral tablets over several weeks. After 10-14 weeks of this initial treatment, patients are randomly assigned to either continue immunotherapy drugs alone or to also have kidney surgery followed by the same drugs. Surgery may be done by different methods and must occur within 8 weeks of randomization. Axitinib is stopped at least 24 hours before surgery. During the study, participants undergo regular scans of the chest, abdomen, and pelvis to assess disease status. They are monitored for survival for up to 7 years after randomization, with follow-up visits every 3 months in the first year, then every 6 months for two years, and annually thereafter. Researchers also evaluate tumor response, surgical complications, and drug side effects. Specimens are collected for future research, and participants' health and treatment effects are closely followed throughout the study period.

Researchers are evaluating whether breast conservation surgery combined with endocrine therapy can achieve a similar rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation surgery followed by breast radiation and endocrine therapy in patients with Stage I, hormone sensitive, HER2-negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial builds on the established role of radiation after lumpectomy, aiming to identify if radiation can be safely omitted in certain low-risk patients to reduce treatment burden and side effects. Participants receive either breast radiation plus endocrine therapy or endocrine therapy alone. Radiation therapy involves external beam radiation to the whole breast with or without a boost, partial breast irradiation, or accelerated partial breast irradiation, starting within 12 weeks after the last breast surgery. Endocrine therapy is given for a minimum of 5 years, with the specific drug choice and schedule determined by the treating physician. Endocrine therapy may begin before, during, or after radiation therapy, depending on the treatment group. Throughout the study, participants undergo regular assessments including imaging such as mammograms or MRI within six months before enrollment, and clinical evaluations to monitor tumor recurrence. The main outcome measured is the time to invasive or non-invasive ipsilateral breast tumor recurrence over five years. Safety, adherence to therapy, and recovery from surgery are also monitored. The total participation period includes at least five years to evaluate long-term recurrence rates.

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 the addition of the immunotherapy drug atezolizumab to standard chemotherapy treatment for patients with poorly differentiated extrapulmonary neuroendocrine carcinoma that is advanced, metastatic, unresectable, or recurrent. This phase II/III trial aims to compare the effects of combining atezolizumab with platinum-based chemotherapy (cisplatin or carboplatin) and etoposide against standard chemotherapy alone. The study also compares the use of atezolizumab only during initial treatment versus continuing it beyond induction treatment. Participants are randomly assigned to one of three groups. In Arm 1, patients receive induction treatment with atezolizumab plus platinum chemotherapy and etoposide every 21 days for four cycles, followed by maintenance atezolizumab every 21 days for up to 17 cycles. In Arm 2, patients receive the same induction treatment but then undergo observation for one year without maintenance therapy. In Arm 3, patients receive platinum chemotherapy and etoposide only for four cycles followed by observation for one year. All treatments are given intravenously. Patients also have blood samples collected and undergo CT scans and/or MRI scans during the trial. Throughout the study, participants are monitored with imaging and blood tests to assess their response and safety. After completing treatment, patients are followed for up to five years to measure overall survival and other outcomes like progression-free survival, response rates, and safety. The study also collects tumor and blood samples for future biomarker research.

Researchers are evaluating the Galleri4 multi-cancer early detection (MCED) test in a multi-center prospective cohort study involving the Medicare population aged 50 years and older. This study aims to understand the real-world clinical impact of the test, including its safety and how well it detects cancers early. The study seeks to enroll participants who represent the Medicare population, including those with Traditional Medicare or Medicare Advantage coverage. Participants in the study are divided into two groups: one group receives the Galleri test through blood collection and multi-cancer early detection testing with return of results, while the other group receives usual care without the Galleri test. The study excludes individuals who have previously had an MCED test, are undergoing clinical evaluation for suspected cancer, have certain recent or untreated cancer histories, are pregnant, or are currently inpatient at a participating site. The study is designed to monitor participants over time without specifying a maximum age limit. During the study, researchers will track the incidence rates of stage IV cancers over a period of up to 3 years. Participants will be monitored for safety and test performance outcomes. The study involves informed consent from participants who are capable of providing it directly, and it excludes those who cannot comply with study procedures or who are not registered patients at participating centers. This research aims to provide data on the effectiveness and safety of the Galleri test in a real-world Medicare population setting.

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.