Poulsbo

This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. The study consists of three parts (Part 1, Part 2, and Part 3) along with the Japan and China monotherapy cohorts. Part 1 and Part 2 are closed for enrollment. Part 1 tested monotherapy in 3 cohorts (Parts 1A, 1B, and 1C); Part 2 tested combination therapy in Parts 2A (dose escalation), 2B and 2C (does expansion). Part 3 consists of the Bioequivalence (BE) and drug-drug interaction (DDI) substudies and are open for enrollment. The BE substudy will test between 2 mevrometostat formulation to confirm that they work in the body the same way. The DDI substudy will evaluate the effect of a strong CYP3A4 (an enzyme in your body that breaks down/ removes drugs) inhibitor on the PK of mevrometostat; a strong CYP3A4 inhibitor may slow down the breakdown/ removal of drugs in your body. The Sponsor may choose to delay or discontinue any cohorts or substudies.

Researchers are evaluating how well active surveillance helps doctors monitor patients with low-risk germ cell tumors after surgical removal. The study also compares chemotherapy treatments using carboplatin versus cisplatin in pediatric, adolescent, and young adult patients with metastatic standard risk germ cell tumors. It aims to determine overall survival, event-free survival, and side effects such as hearing loss among these patients. The study includes patients with low-risk stage I ovarian immature teratoma or stage I non-seminoma or seminoma germ cell tumors who undergo observation. Patients with standard risk tumors are randomly assigned to receive one of four chemotherapy regimens combining bleomycin, etoposide, carboplatin, or cisplatin, given intravenously on specific days over cycles repeating every 21 days. Treatments continue for up to 3 or 4 cycles if no disease progression or unacceptable side effects occur. Throughout treatment and observation, patients undergo imaging scans, blood sample collection, tumor biopsies if needed, and pulmonary function tests. Participants will be followed with regular imaging and blood tests to monitor tumor response and recurrence, including CT, MRI, and chest x-rays. Follow-up visits occur every 2 months for the first year, then every 3 to 6 months through year 2, every 6 months for years 3 to 5, and annually up to 10 years. The study also assesses hearing outcomes, body composition, tumor marker decline, neuropathy, and serum microRNA over time to better understand treatment effects and patient quality of life.

This research aims to collect data and samples from patients who experience side effects from immunotherapy used in cancer treatment. The goal is to better understand, predict, prevent, and treat these immune-related side effects, including serious adverse events, rare infections, or accelerated tumor growth. This observational study is led by the Alliance for Clinical Trials in Oncology and focuses on patients treated with immuno-oncology therapies who have experienced significant immune-related adverse events. Participants provide tissue and blood samples, with optional stool samples for those experiencing colitis, within 72 hours of confirming a serious immune-related adverse event and again one month later. The study also includes a review of patients' medical records for up to one year. This approach helps establish a national biorepository of biospecimens and clinical data for future research. During the study, participants will undergo sample collection at two time points and have their medical history reviewed over a year. Researchers will monitor the establishment of the biorepository and collect clinical data to support future studies. This process aims to improve knowledge about immune-related side effects from immunotherapy and contribute to better patient care over time.

Researchers are investigating treatments for patients with high-risk smoldering multiple myeloma, a condition where abnormal plasma cells grow in the bone marrow but without symptoms. This phase III trial evaluates how well lenalidomide and dexamethasone work together, with or without the addition of daratumumab, an immunotherapy drug. The study aims to compare overall survival, progression-free survival, response rates, and quality of life between these two treatment approaches. Participants are randomly assigned to one of two treatment groups. One group receives daratumumab intravenously on a set schedule alongside oral lenalidomide daily and dexamethasone on specific days within repeated 28-day cycles, up to 24 cycles. The other group receives lenalidomide and dexamethasone on a similar schedule without daratumumab. Treatment continues until disease progression or unacceptable side effects occur. After treatment, patients are followed up for up to 15 years to monitor long-term outcomes. Throughout the study, participants undergo evaluations including blood and urine tests, bone marrow biopsies, and imaging scans such as FDG-PET/CT. Researchers assess treatment response, minimal residual disease status, safety, and quality of life using questionnaires. They also monitor treatment adherence and side effects, including infusion reactions. The main outcomes measured are overall survival and changes in quality of life. Safety and various laboratory and imaging markers are regularly reviewed to understand treatment effects and disease progression.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase II/III 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 outcomes of two treatments for lumbar spinal stenosis with neurogenic claudication (LSS with NC) in Medicare beneficiaries. This observational study compares the rates of surgical and minimally invasive interventions, as well as any harms, occurring within 24 months after receiving either the MILD procedure or Interspinous Process Decompression (IPD). The study uses Medicare claims data starting from patients treated on or after January 1, 2017, and continues enrollment until the sponsor stops it. The study groups include Medicare patients who underwent the MILD procedure, which involves a partial decompression performed under fluoroscopic image guidance through the removal of tissue and bone at the symptomatic spinal level. The control group consists of Medicare patients treated with Interspinous Process Decompression during the same enrollment period. Both groups are monitored for reoperation and harms for 24 months following their initial treatment. Participants are included based on Medicare claims with the study's NCT number, which automatically enrolls them without requiring prior consent. Researchers will analyze Medicare claims data to track surgical or minimally invasive interventions and any complications related to the initial procedure over two years. The study does not involve direct patient visits or interventions and is exempt from Institutional Review Board oversight. The total follow-up duration for outcome measurement is 24 months after the index procedure.

Researchers are evaluating the combination of bevacizumab and osimertinib versus osimertinib alone as an initial treatment for patients with advanced non-small cell lung cancer (NSCLC) that has spread beyond the lungs and has specific mutations in the EGFR gene. This phase III trial aims to understand if adding bevacizumab, which inhibits blood vessel growth to tumors, can control cancer longer and improve survival compared to osimertinib alone, which blocks EGFR involved in tumor cell growth. Participants are randomly assigned to one of two groups. One group receives daily oral osimertinib every 21 days, while the other group receives the same osimertinib dose plus an intravenous bevacizumab infusion every 21 days. Treatment continues until disease progression or unacceptable side effects occur. During the study, patients undergo various imaging tests such as echocardiography, multigated acquisition scan, computed tomography, and possibly magnetic resonance imaging, along with blood and urine sample collections. After treatment ends, patients are followed every three months for up to 10 years to monitor their health and disease status. The main outcome measured is progression-free survival, tracking the time until the cancer worsens or death occurs. Secondary outcomes include overall survival, response rates, and effects on central nervous system progression. Safety is also assessed through adverse event monitoring. This long-term follow-up helps researchers understand the lasting effects of the treatments.

Researchers are evaluating the effectiveness of radiation therapy with or without the chemotherapy drug cisplatin in treating patients who have stage III-IVA squamous cell carcinoma of the head and neck and have undergone surgery. This phase II trial aims to understand how well these treatments work, focusing on disease-free survival and the role of p53 gene mutations in predicting patient outcomes. The study also examines treatment side effects and explores genetic changes that could guide new therapies. Participants are randomly assigned to one of two treatment groups. One group receives intensity-modulated radiation therapy (IMRT) once daily, five days a week for six weeks. The other group receives the same radiation schedule combined with weekly intravenous cisplatin over 1-2 hours for six weeks. After treatment, patients will be followed up every six months for three years and then annually for seven more years to monitor their health status and disease progression. Throughout the study, participants undergo various assessments including surgical tissue analysis for p53 mutations, imaging tests to check for disease spread, and regular evaluations of treatment side effects. Researchers measure disease-free survival, tracking the time until cancer recurrence, new tumors in the head and neck region, or death for up to ten years. Safety is monitored closely during treatment, with adverse events recorded up to six weeks after therapy. The total participation duration can extend up to ten years due to long-term follow-up.

Researchers are evaluating the effectiveness of ramucirumab combined with paclitaxel versus the FOLFIRI regimen (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) in treating patients with advanced or treatment-resistant small bowel adenocarcinoma. Ramucirumab is a monoclonal antibody that targets VEGFR-2 to potentially reduce tumor blood supply and growth. Chemotherapy drugs like paclitaxel, leucovorin calcium, fluorouracil, and irinotecan work by stopping tumor cell growth through different mechanisms. Participants are randomly assigned to one of two treatment groups. In the first group, patients receive ramucirumab intravenously over 30-60 minutes on days 1 and 15, and paclitaxel intravenously over 30 minutes on days 1, 8, and 15, with each cycle lasting 28 days. In the second group, patients receive irinotecan intravenously over 90 minutes on days 1 and 15, leucovorin intravenously over 2 hours on days 1 and 15, and fluorouracil both as an IV bolus on days 1 and 15 and continuously over 46-48 hours on days 1-3 and 15-17. Treatment cycles repeat every 28 days unless disease progresses or side effects become unacceptable. During the study, patients are monitored with assessments every 8 weeks until their disease progresses. After progression, follow-up continues every 6 months for up to 3 years. Researchers measure progression-free survival, overall response rate, overall survival, and track any adverse events. Tissue and blood samples are also collected for future research. Patient safety and treatment effects are carefully evaluated throughout the study.

Researchers are evaluating patients with metastatic HER-2-positive breast cancer who are receiving trastuzumab-based therapy and are at risk of heart problems. The study includes two groups: one large observational group taking beta blockers, ACE inhibitors, or ARBs alongside trastuzumab, and a smaller randomized group comparing the effects of carvedilol versus no treatment. The aim is to understand the occurrence of heart issues and whether carvedilol might help prevent cardiac side effects from chemotherapy. Participants are assigned to one of three arms based on their current medications. Patients not on beta blockers, ARBs, or ACE inhibitors are randomized to either receive carvedilol orally twice daily or no study intervention. Those already taking these heart medications enter an observational arm without additional treatment. Treatment and observation continue for up to 108 weeks unless disease progression or unacceptable side effects occur. Throughout the study, participants undergo heart function monitoring with echocardiograms every 12 weeks and provide blood samples for biomarker analysis. Researchers track the time to the first sign of heart dysfunction and any cardiac events, as well as adherence to medication and side effects. The study also collects data to develop models predicting heart risk and banks samples for future research. Participant involvement may last over two years with regular assessments to monitor safety and heart health.