Pittsburgh, PA Paid Clinical Trials

This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT. Read Less

This phase II trial tests whether atezolizumab in combination with selinexor works to shrink tumors in patients with alveolar soft part sarcoma and whether the study drugs are better than the usual approach in treating this type of cancer. The usual approach is defined as care most people get for alveolar soft part sarcoma if they are not part of a clinical study, which includes treatment with radiation, kinase inhibitor drugs, immunotherapy drugs, or chemotherapy drugs. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may help keep cancer cells from growing and may kill them. Giving atezolizumab in combination with selinexor may help shrink tumors and stabilize the cancer in patients with alveolar soft part sarcoma. Read Less

This phase II ComboMATCH treatment trial compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had progression of cancer after previous treatments (2nd line setting). Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by killing tumor cells. Leucovorin may help the other drugs in the mFOLFOX6 chemotherapy regimen work better by making tumor cells more sensitive to the drugs. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps to stop or slow the spread of tumor cells. Giving binimetinib in combination with mFOLFOX6 chemotherapy may be effective in shrinking or stabilizing advanced biliary tract cancers in the 2nd line setting. Read Less

The purpose of this study is to determine whether BHV-7000 is effective in the treatment of idiopathic generalized epilepsy with generalized tonic-clonic seizures and includes an additional open-label extension (OLE) phase. Read Less

This phase II ComboMATCH treatment trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers. Palbociclib and binimetinib are both in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals cancer cells to multiply. This trial may help researchers understand if giving the combination of palbociclib and binimetinib can help improve the amount of time before the cancer grows in patients with patients with low grade serous ovarian cancer who have certain changes in the tumor DNA. This trial may also help researchers understand if giving the combination of palbociclib and binimetinib can help improve outcomes among patients with low grade serous ovarian cancer who have previously received a MEK inhibitor. For patients with other tumors, with the exception of lung cancer, colon cancer, melanoma and low grade serous ovarian cancers, this trial may help researchers understand if giving the combination of palbociclib and binimetinib can improve the clinical outcome of survival without progression in patients who have certain changes in their tumor's DNA. Read Less

Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Increasingly, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class - (cblC, cblD, cblF, cblJ and cblX) - and are also heterogenous, clinically and biochemically. The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature (hyper)homocysteinemia. Lastly, a group of patients can have increased methylmalonic acid and/or homocysteine in the blood or urine caused by variant(s) in recently identified (ACSF3) and unknown genes. In this protocol, we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last up to 4-5 days and involve urine collection, blood drawing, ophthalmological examination, radiological procedures, MRI/MRS, skin biopsies in some, and developmental testing. In a subset of patients who have or will receive renal, hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA, a lumbar puncture to examine CSF metabolites will be performed. In this small group of patients, CSF metabolite monitoring may be used to adjust therapy. The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies, query for genotype/enzymatic/phenotype correlations, search for new genetic causes of methylmalonic acidemia and/or homocysteinemia, identify new disease biomarkers and define clinical outcome parameters for future clinical trials. The population will consist of participants previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acidemia Association, Homocystinuria Network America and other national and international support groups. Most participants will be evaluated only at the NIH Clinical Center. However, if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol, that patient may enroll at the Children's National Medical Center (CNMC) site, pending approval by Dr Chapman, the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children's Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters.... Read Less

The goal of the study is to collect data on patients treated outside of a clinical trial (in routine clinical practice) with standard of care osimertinib with or without chemotherapy in Epidermal Growth Factor Receptor (EGFR)-mutant Non-Small Cell Lung Cancer (NSCLC) to better understand the safety and effectiveness of these standard of care regimens. Read Less

The goal of this study is to compare how well sonrotoclax plus obinutuzumab works versus venetoclax plus rituximab in treating adults with relapsed and/or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study will also compare how well sonrotoclax plus rituximab works versus venetoclax plus rituxumab in treating adults with R/R CLL/SLL. The safety of these treatments will also be assessed. Read Less

The purpose of this clinical research study is to learn more about the use of the study medicine, volixibat, for the treatment of pruritus (itching) associated with Primary Sclerosing Cholangitis (PSC), and to assess the possible impact on the disease progression of PSC. Read Less

This study is open to adults with type 2 diabetes, high blood pressure, and cardiovascular disease. People can join the study if they have these conditions and do not have a history of heart failure. The purpose of this study is to find out if a medicine called vicadrostat, when taken with empagliflozin, helps reduce cardiovascular risk in people with these conditions. The study will compare this combination to a placebo version of vicadrostat with empagliflozin. Participants are put into 2 groups randomly, which means by chance. One group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets with empagliflozin. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take a tablet once per day for 2 and a half years and up to 4 years and 3 months. All participants also continue their medication for type 2 diabetes, high blood pressure, and cardiovascular disease. Participants have an equal chance of receiving the study medicine or placebo. Participants are in the study for up to 4 years and 3 months. During this time, they visit the study site regularly. During these visits, doctors collect information about participants' health and take blood samples. The doctors document when participants experience cardiovascular events. The doctors also regularly check participants' health and take note of any unwanted effects. Read Less

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment with capecitabine in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and that it has progressed on previous standard treatment. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Capecitabine is in a class of medications called antimetabolites. It is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors. Read Less

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of sacituzumab tirumotecan with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for sacituzumab tirumotecan in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study. Read Less