McKeesport

Researchers are evaluating the effects of adding cemiplimab, an immunotherapy drug that blocks the PD-1 pathway to help the immune system attack tumor cells, to the usual treatment of docetaxel and ramucirumab in patients with stage IV or recurrent non-small cell lung cancer. This phase II/III Expanded Lung-MAP trial compares cemiplimab combined with docetaxel and ramucirumab versus docetaxel and ramucirumab alone, aiming to improve treatment outcomes in patients who previously received platinum chemotherapy and immunotherapy but developed resistance or disease progression. Participants are randomly assigned to one of two treatment arms. In Arm I, patients receive dexamethasone orally twice daily on days 0-2, ramucirumab and docetaxel intravenously on day 1 of each 21-day cycle. In Arm II, patients receive the same treatments plus cemiplimab intravenously on day 1 of each cycle. Treatment cycles continue every 21 days until disease progression or unacceptable side effects occur. Throughout the study, patients undergo regular blood sample collection and imaging scans such as CT or MRI to monitor disease status. During the study, participants are closely monitored with scans, blood tests, and physical exams to assess overall survival and other outcomes like progression-free survival, response rates, and treatment safety. Researchers also collect blood samples for future molecular studies. After completing treatment, patients are followed up every 3 to 6 months for up to 3 years to track long-term survival and health status. The study measures overall survival from randomization to death from any cause, assessed up to 3 years.

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 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 effectiveness of radiation therapy with or without the chemotherapy drug cisplatin in patients with stage III-IVA squamous cell carcinoma of the head and neck who have had surgery to remove their tumors. This phase II trial aims to understand if adding cisplatin to radiation therapy improves disease-free survival, especially considering the role of p53 mutations in the cancer cells. The study also investigates toxicities and potential genomic factors that might influence treatment outcomes. Patients are randomly assigned to one of two treatment groups. One group receives intensity-modulated radiation therapy (IMRT) alone once daily, five days a week for six weeks. The other group receives the same radiation treatment combined with weekly intravenous cisplatin over one to two hours, also for six weeks. Treatment continues as long as there is no disease progression or unacceptable side effects. During the study, participants undergo regular follow-ups every six months for three years and then yearly for seven more years to monitor for cancer recurrence or new tumors. Researchers assess disease-free survival, tracking the time from randomization until cancer returns, a second tumor develops, or death. Additional laboratory tests and biomarker analyses are performed to understand genetic changes and treatment effects. Safety and toxicities are closely monitored throughout the study period.

Researchers are evaluating the effectiveness of using brain magnetic resonance imaging (MRI) scans alone compared to combining MRI scans with prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC). This phase III trial aims to determine if MRI surveillance alone is not worse than adding PCI in terms of overall survival. The study also looks at cognitive function, brain metastasis-free survival, and treatment side effects among patients with limited or extensive-stage SCLC. Participants are randomly assigned to one of two groups. One group receives PCI, which is radiation therapy focused on the brain, given over two weeks for 20 minutes per day, five days a week, along with scheduled MRI scans at 3, 6, 9, 12, 18, and 24 months. The other group undergoes MRI scans at the same intervals without receiving PCI. Both groups are monitored closely through these MRI scans to track any spread of cancer to the brain. During the study, patients will have regular MRI scans, cognitive assessments, and evaluations of side effects and survival outcomes up to two years after randomization. Blood samples will be collected for future research. Researchers will monitor overall survival, cognitive failure rates, and brain metastasis occurrence, aiming to understand if avoiding PCI might reduce side effects without compromising survival. Participant involvement includes multiple scheduled scans and tests over a two-year follow-up period.

Researchers are evaluating whether 6 months of human epidermal growth factor receptor 2 (HER2)-targeted therapy is as effective as 12 months of the same treatment for patients with early-stage HER2-positive breast cancer who have no remaining invasive cancer after preoperative chemotherapy with trastuzumab. This phase III trial focuses on patients who achieved a pathologic complete response (pCR), aiming to assess recurrence-free survival and quality of life outcomes. The study also explores differences in side effects and survival among subgroups based on treatment delivery and hormone receptor status. Participants are randomly assigned to receive either 6 or 12 months of HER2-targeted therapy, including trastuzumab and possibly pertuzumab, administered intravenously or subcutaneously every 21 days. The treatment cycles continue up to 9 or 17 cycles respectively, unless disease progression or unacceptable side effects occur. Throughout the trial, patients undergo regular heart function tests (echocardiography or MUGA), breast imaging (mammography, ultrasound, or MRI), and may optionally provide blood and tissue samples. During the study, patients complete quality of life questionnaires and are monitored for cancer recurrence and side effects. Follow-up visits occur every 6 months for 5 years and then annually up to 10 years after registration. The main outcomes measured include time without cancer recurrence and patient-reported quality of life at 12 months. Safety and long-term effects of the different treatment durations are also assessed.

Researchers are evaluating the effectiveness of radiation therapy combined with chemotherapy and immunotherapy in patients with high-risk stage III-IV squamous cell carcinoma of the head and neck that is HPV-negative. The study aims to compare the usual treatment of radiation therapy with cisplatin chemotherapy against two experimental approaches: radiation with docetaxel and cetuximab chemotherapy, and the usual treatment plus the immunotherapy drug atezolizumab. This phase II/III trial focuses on improving disease-free and overall survival in this patient population. Participants are randomly assigned to one of three treatment groups. One group receives intensity-modulated radiation therapy (IMRT) with weekly cisplatin for 6 weeks. Another group receives IMRT with weekly docetaxel and cetuximab. The third group receives IMRT with weekly cisplatin plus atezolizumab administered intravenously every 3 weeks starting one week before radiation, for up to eight doses. Treatments are given in the absence of disease progression or unacceptable side effects. Throughout the study, patients undergo blood sample collection and may have CT scans, MRI, and biopsies as needed. Follow-up visits occur at 1 and 3 months post-treatment, then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter. Researchers measure disease-free survival up to 7 years, overall survival up to 7 years, symptom burden, quality of life, and treatment-related toxicities. Blood and tissue specimens are collected for future research.

Researchers are evaluating whether combining two immunotherapy drugs, nivolumab and ipilimumab, is more effective than nivolumab alone in shrinking tumors for women with recurrent endometrial carcinoma that has a deficient mismatch repair system (dMMR). This phase II trial focuses on patients whose cancer returned after a period without detectable disease. Deficient mismatch repair in tumor cells, which can be linked to genetic conditions like Lynch Syndrome, may make cancers more responsive to immunotherapy. Participants are randomly assigned to one of two treatment groups. One group receives nivolumab intravenously every three weeks and ipilimumab every six weeks for up to eight cycles; afterward, they continue nivolumab alone every four weeks. The other group receives nivolumab alone every three weeks for up to eight cycles, then every four weeks afterward. Patients who achieve a complete response continue nivolumab for an additional 12 months as maintenance therapy. Optional tissue and blood samples are collected during the trial, and imaging scans like CT or MRI are performed regularly. During the study, patients are monitored with scans and laboratory tests to assess their response and safety. Researchers measure progression-free survival up to five years after randomization, along with overall survival, response rates, and side effects. Follow-up visits occur every three months for two years, then every six months for three more years to track long-term outcomes and safety.