This is an open-label, multicenter, phase II basket study of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring rat sarcoma virus (RAS), a member of the rapidly accelerated fibrosarcoma (non-V600 BRAF), extracellular signal-regulated kinase (ERK), or mitogen-activated protein kinase (MEK) mutations. The trial will have five baskets based on disease primary as listed below.~Basket 1: Cholangiocarcinoma including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, or extrahepatic cholangiocarcinoma;~Basket 2: Pancreatic adenocarcinoma;~Basket 3: Colorectal adenocarcinoma;~Basket 4: Esophageal adenocarcinoma, esophageal squamous cell carcinoma, or gastroesophageal junction (GEJ) adenocarcinoma;~Basket 5: Gastric adenocarcinoma.~While the overall trial is a basket design, each basket will operate as a Simon two-stage design and therefore, will open to enrollment in two-stages.~Total enrollment for Stage 1 is targeted at approximately 65 patients with 13 patients per group. Additional patients may be enrolled as appropriate.~Total enrollment for Stage 2 is targeted to approximately 150 patients with up to 30 patients per group. Additional patients may be enrolled as appropriate.
This is an open-label, prospective phase two basket trial assessing the efficacy of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies. All patients enrolled must have a mitogen-activated protein kinase (MAPK) activating mutation to be deemed eligible for trial participation. Each disease-based basket will open to enrollment in two-stages. The opening of stage two will be dependent on the observed responses in the patients enrolled in the first stage.