Title
A Phase 1 Clinical Trial of CA-4948 in Combination with Gemcitabine and NabPaclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma

Description
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.

Objective
PRIMARY OBJECTIVE:

I. To assess dose limiting toxicities and determine the recommended phase 2 dose of emavusertib (CA--4948) in combination with chemotherapy in patients with pancreatic ductal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To evaluate the safety and tolerability of the combination of CA-4948 and chemotherapy.

III. To determine preliminary signals of efficacy, as measured by objective response rate (ORR), CA-4948 response, progression free survival (PFS), and overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To evaluate pharmacodynamic effect of CA-4948 in combination with chemotherapy.

II. To evaluate pharmacokinetics of CA-4948 in combination with chemotherapy. III. To explore biomarkers and genomic alterations associated with treatment response.

Treatment Procedure: Biopsy
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Biological: Emavusertib
Drug: Gemcitabine Hydrochloride
Procedure: Magnetic Resonance Imaging
Drug: Nab-paclitaxel
Procedure: Positron Emission Tomography
Procedure: X-Ray Imaging

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Pancreas

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital