Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies
brief summary
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.
detailed description
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.
official title
A Phase 2 Basket Trial of Ulixertinib (BVD-523) in Combination With Hydroxychloroquine in Patients With Advanced GI Malignancies Harboring Mitogen-activated Protein Kinase (MAPK) Pathway Mutations (BVD-523-HCQ)