Mooresville

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 how factors like age, gender, other medical conditions, and the type of immunotherapy affect the development of side effects in patients with malignant solid tumors receiving immune checkpoint inhibitor (ICI) therapy. The study aims to develop and validate a risk prediction model for serious immune-related side effects during the first year of ICI treatment. Additional goals include tracking the occurrence of various side effects, quality of life, patient-reported symptoms, and treatment patterns over 12 months, along with studying biological markers that may predict side effect risk. Participants will have tissue samples collected at the start of their cancer treatment and will complete questionnaires at baseline and at weeks 4, 12, 24, and 52. Blood samples may also be collected at multiple times during the study. The study focuses on patients receiving standard-of-care ICI therapy for solid tumors, without combination chemotherapy or other non-ICI treatments. During the study, participants will complete patient-reported outcome forms and health questionnaires to assess side effects and quality of life. Researchers will monitor the occurrence of severe immune-related side effects over 52 weeks and evaluate biological markers from blood and tissue samples. The study also assesses the use of electronic methods for collecting patient data. Total participation includes assessments over approximately one year following treatment start.

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 surgical and minimally invasive treatments for lumbar spinal stenosis (LSS) by comparing Medicare patients who received the MILD procedure against those who had interspinous process decompression (IPD). The study focuses on outcomes such as the rate of harms related to the initial procedure and the frequency of additional surgical or minimally invasive interventions within 24 months after treatment. Enrollment includes patients treated from January 1, 2017, onward, with continuation until the sponsor decides to stop. The MILD procedure involves percutaneous image-guided lumbar decompression, performed under fluoroscopy through a dorsal approach to partially remove tissue and bone at the affected spinal level. The control group receives the IPD procedure for LSS. Both groups are monitored for a 24-month period post-index procedure using Medicare claims data to track reoperations and any harms. Participants contribute data through Medicare claims without needing prior enrollment or consent, as the study is exempt from IRB oversight. Researchers collect and analyze information on procedure-related harms and subsequent interventions over two years. This approach allows evaluation of long-term safety and effectiveness outcomes for patients treated with either MILD or IPD.

Researchers are studying patients with metastatic HER-2-positive breast cancer who are receiving trastuzumab-based treatments to understand the risk of heart problems related to their cancer therapy. The study includes two groups: one large observational group of patients already taking beta blockers, ACE inhibitors, or ARBs alongside their cancer treatment, and a smaller randomized group comparing patients who receive carvedilol, a heart medication, to those who do not. The trial aims to assess how often heart issues occur and whether carvedilol can help prevent heart damage from chemotherapy. It also investigates biomarkers and heart function measures as predictors of cardiac risk. In the randomized part, patients not already on beta blockers, ACE inhibitors, or ARBs are assigned to receive carvedilol twice daily or no additional treatment for up to 108 weeks, with treatment cycles repeated every 12 weeks if there is no disease progression or unacceptable side effects. Patients already taking these heart medications join the observational cohort and are monitored for up to 108 weeks without any change in their therapy. The study collects blood samples and performs regular heart imaging to evaluate heart function and strain. Participants will have regular echocardiograms every 12 weeks to monitor heart function, with both local and central readings compared. Blood samples are collected for biomarker analysis, and patient health status is assessed throughout the study. The main outcome measured is the time until any heart dysfunction is first detected, followed for up to 108 weeks. The study also tracks interruptions in cancer therapy due to heart problems and explores genetic and plasma markers that might predict heart risk. Participants are followed closely for safety and treatment effects during the entire study period.

Researchers are evaluating how well serum tumor marker directed disease monitoring (STMDDM) works for patients with hormone receptor positive, HER2 negative metastatic breast cancer. The study compares STMDDM with the usual care approach to see if overall survival is not worse using STMDDM. The trial also looks at healthcare costs, patient anxiety, quality of life, and preferences related to disease monitoring. Patients are randomly assigned to one of two groups. One group receives usual care with imaging at least every 12 weeks and other monitoring at the doctor's discretion for up to 312 weeks if the disease does not progress. The other group has their serum tumor markers checked every 4 to 8 weeks, with imaging only if markers are elevated, also for up to 312 weeks without progression. Additional assessments include quality-of-life and anxiety questionnaires. Throughout the study, participants undergo regular evaluations including imaging, blood tests for tumor markers, and patient-reported outcome questionnaires. Researchers track overall survival up to 312 weeks after randomization, along with healthcare costs and patient experiences. Participants must provide informed consent and are monitored for safety during the study period.

Researchers are evaluating whether adding pembrolizumab, a type of immunotherapy, to usual chemotherapy improves outcomes in patients with stage IIA, IIB, IIIA, or IIIB non-small cell lung cancer that has been removed by surgery. Pembrolizumab may help the immune system attack cancer cells and prevent tumor growth. Chemotherapy drugs like cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel work by stopping tumor cells from growing and spreading. This phase III trial compares disease-free survival between different treatment approaches involving pembrolizumab and chemotherapy. Participants are randomly assigned to one of two treatment groups. In Arm B, patients receive four cycles of chemotherapy followed by pembrolizumab given intravenously every 21 days for up to 17 cycles or every 6 weeks for 16 cycles. In Arm C, patients receive chemotherapy combined with pembrolizumab during the initial four cycles, followed by pembrolizumab alone for up to 13 cycles every 21 days or 12 cycles every 6 weeks. Chemotherapy regimens include various platinum doublets chosen by the treating physician. Arm A was closed as of February 2022. Patients may also undergo tests such as echocardiograms, MRIs, CT scans, and blood sample collections during the trial. Throughout the study, participants are monitored with regular assessments including imaging and blood tests. Follow-up visits occur 6 weeks after treatment, then every 3 months for 2 years, every 6 months for years 2-4, and annually up to 10 years after randomization. Researchers measure disease-free survival, overall survival, adverse events, drug discontinuation rates, and patient quality of life using questionnaires. The study also explores outcomes based on tumor markers like PD-L1 expression and tumor mutational burden.

PRIMARY OBJECTIVES: I. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial cancer. SECONDARY OBJECTIVES: I. To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial cancer. II. To evaluate the overall response rate (ORR) in patients with measurable disease. III. To evaluate the duration of objective response in patients with measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. IV. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 for each treatment arm. V. To compare quality of life (QOL), as measured by Functional Assessment of Cancer Therapy - Endometrial Trial Outcome Index (FACT-En-TOI), in the experimental versus control arms. VI. To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the Patient Reported Outcomes (PRO) - CTCAE, patient-reported fatigue as measured with the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue short form, and worry concerning side effects of treatment as measured by the item 'bothered by side effect', in the FACT-En TOI, respectively, in the experimental and control arms. VII. To assess the correlation of HER2 immunohistochemistry (IHC) expression and in situ hybridization (ISH) amplification with clinical outcome and response to HER2 targeted therapies. EXPLORATORY OBJECTIVE: I. To explore time to sustained deterioration in quality of life, as measured by a drop in the FACT-En-TOI by 6 or more points lasting for more than one PRO time point, in the experimental and control arms. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. ARM II: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and trastuzumab/hyaluronidase-oysk subcutaneously (SC) over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive trastuzumab/hyaluronidase-oysk SC over 2-5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance therapy for up to 3 years from the start of treatment. ARM III: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30-60 minutes, and pertuzumab/trastuzumab/hyaluronidase-zzxf SC over 5-8 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease after completion of cycle 6 may receive 4 additional cycles of this treatment at the discretion of the treating physician. MAINTENANCE: Patients receive pertuzumab/trastuzumab/ hyaluronidase-zzxf SC over 5 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in absence of disease progression or unacceptable toxicity. Patients with SD or PR may continue maintenance for up to 3 years from the start of treatment. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) throughout the study. Additionally, patients may optionally undergo blood sample collection throughout the study, vaginal brachytherapy on study, and urine sample collection prior to treatment. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Researchers are evaluating whether adding stereotactic ablative radiation therapy (SABR) to standard immunotherapy improves outcomes for patients with metastatic renal cell cancer that cannot be removed by surgery. This phase II trial compares the combination of SABR and immunotherapy to immunotherapy alone. Immunotherapy drugs include monoclonal antibodies like nivolumab, ipilimumab, avelumab, pembrolizumab, and targeted therapies such as axitinib, cabozantinib, and lenvatinib. The study aims to assess kidney removal and radiographic progression-free survival as the main outcome. Participants are randomly assigned to one of two groups. One group receives immunotherapy alone, with different drug combinations given intravenously or orally as chosen by the doctor. The other group receives SABR treatment delivered in three sessions over 1 to 3 weeks alongside the same immunotherapy regimens. SABR uses high-precision radiation to target tumors with fewer doses and less damage to healthy tissue. Both groups undergo regular scans such as CT or MRI and may have bone scans and blood samples taken throughout the trial. After completing treatment, patients are followed up every six months for five years, then yearly for three more years. Researchers monitor outcomes including tumor response, disease progression, safety, side effects, survival, and biomarkers from tissue and blood samples. The study also evaluates effects on blood vessel tumors and the response of non-irradiated tumors. Total participation may last up to eight years with ongoing assessments to understand long-term benefits and risks.