Brief Summary
This phase I trial tests the safety, side effects, and best dose of emavusertib (CA-4948) in combination with gemcitabine and nab-paclitaxel in treating patients with pancreatic ductal adenocarcinoma that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). CA-4948 is in a class of medications called kinase inhibitors. It works by blocking the action of abnormal proteins called interleukin-1 receptor-associated kinase 4 (IRAK4) and FMS-like tyrosine kinase 3 (FLT3) that signal cells to multiply. This may help keep cancer cells from growing. The usual approach for patients with pancreatic ductal adenocarcinoma is treatment with chemotherapy drugs gemcitabine and nab-paclitaxel. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Giving CA-4948 in combination with gemcitabine and nab-paclitaxel may shrink or stabilize metastatic or unresectable pancreatic ductal adenocarcinoma.
Protocol Interventions
Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Emavusertib, Drug: Gemcitabine Hydrochloride, Drug: Nab-paclitaxel
Brief Summary
This study is Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors
Protocol Interventions
Drug: [203Pb]VMT-α-NET, Drug: [212Pb]VMT-α-NET
Brief Summary
This trial is a single-arm, prospective, multi-center clinical trial designed to demonstrate that stereotactic adaptive radiotherapy using an ablatively dosed (50Gy,5fx) for treatment of borderline-resectable, locally-advanced , or medically inoperable pancreatic adenocarcinoma will translate into a decreased toxicity. The study will evaluate GI toxicity, overall survival, local control, quality of life, and workflow metrics.
Protocol Interventions
Radiation: Daily Adaptive External Beam Radiation Therapy
Brief Summary
The purpose of this study is to learn the best approach to treating patients with known or suspected Barrett’s esophagus by comparing endoscopic surveillance to endoscopic eradication therapy.
To diagnose and manage Barrett’s esophagus and low-grade dysplasia, doctors commonly use procedures called endoscopic surveillance and endoscopic eradication therapy. Endoscopic surveillance is a type of procedure where a physician will run a tube with a light and a camera on the end of it down the patients throat and remove a small piece of tissue. The piece of tissue, called a biopsy, is about the size of the tip of a ball-point pen and is checked for abnormal cells and cancer cells.
Endoscopic eradication therapy is a kind of surgery which is performed to destroy the precancerous cells at the bottom of the esophagus, so that healthy cells can grow in their place. It involves procedures to either remove precancerous tissue or burn it. These procedures can have side effects, so it is not certain whether risking those side effects is worth the benefit people get from the treatments.
While both of these procedures are widely accepted approaches to managing the condition, there is not enough research to show if one is better than the other.
Barrett’s esophagus and low-grade dysplasia does not always worsen to high-grade dysplasia and/or cancer. In fact, it usually does not. So, if a patient’s dysplasia is not worsening, doctors would rather not put patients at risk unnecessarily. On the other hand, endoscopic eradication therapy could possibly prevent the worsening of low-grade dysplasia into high-grade dysplasia or cancer (esophageal adenocarcinoma) in some patients. Researchers believe that the results of this study will help doctors choose the safest and most effective procedure for their patients with Barrett’s esophagus and low-grade dysplasia.
This is a multicenter study involving several academic, community and private hospitals around the United States. Up to 530 participants will be randomized. This study will also include a prospective observational cohort study of up to 150 Barrett’s esophagus and low grade dysplasia patients who decline randomization in the randomized control trial but undergo endoscopic surveillance (Cohort 1) or endoscopic eradication therapy (Cohort 2), and are willing to provide longitudinal observational data.
Protocol Interventions
Procedure: Endoscopic Eradication Therapy
Brief Summary
This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm.
Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.
Protocol Interventions
Drug: CA-4948, Biological: Pembrolizumab, Drug: Trastuzumab, Drug: mFOLFOX7
Brief Summary
This study will compare the safety and effects of HAI floxuridine and dexamethasone combined with the standard chemotherapy drugs gemcitabine and oxaliplatin (GemOx) with those of GemOx alone in people with untreated cholangiocarcinoma that cannot be removed with surgery. The researchers want to find out whether the study treatment works better than the standard chemotherapy to delay progression of disease. For the study treatment to be considered better than the standard treatment, the study treatment should increase the time until progression of disease by an average of 3 months, compared with the usual approach.
Protocol Interventions
Drug: Gemcitabine, Drug: Oxaliplatin
Brief Summary
This phase II/III trial studies the usefulness of treatment with nivolumab and ipilimumab in addition to standard of care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Immunotherapy with antibodies, such as nivolumab and ipilimumab, may remove the brake on the body’s immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy and radiation therapy may reduce the tumor size and the amount of normal tissue that needs to be removed during surgery. A combined treatment with nivolumab and ipilimumab, chemotherapy, and radiation therapy might be more effective in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery.
Protocol Interventions
Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Ipilimumab, Biological: Nivolumab
