Fostamatinib

Fostamatinib is a Syk kinase inhibitor currently FDA-approved for chronic idiopathic thrombocytopenia purpura but it has not been studied in PDAC. The investigators hypothesize that Syk inhibition reprograms macrophages to an immunostimulatory phenotype in the tumor microenvironment. Thus, Syk inhibition with fostamatinib in combination with chemotherapy could improve outcomes for patients with PDAC while having a favorable safety profile.

Although immune checkpoint inhibition has transformed the treatment of some solid malignancies, it has made minimal impact in pancreatic ductal adenocarcinoma (PDAC), which is characterized by a profoundly immunosuppressive microenvironment.

Recent published work by the study investigators demonstrated that inhibition of the Syk kinase - alone and in combination with gemcitabine - in preclinical models of PDAC (animal tumor models and human tissues) reprogrammed tumor associated macrophages resulting in enhanced anti-tumor immunity. With this phase Ib study, the investigators aim to expand the preclinical findings to patients with PDAC.

This is a Phase 1b trial evaluating the combination of Fostamatinib, a Syk kinase inhibitor currently FDA-approved for chronic idiopathic thrombocytopenia purpura (ITP), with the standard of care chemotherapy agents gemcitabine and nab-paclitaxel, for the perioperative treatment of resectable non metastatic pancreatic ductal adenocarcinoma (PDAC).

Registro actualizado en ClinicalTrials.gov →

• Patient has the ability to understand and willingness to sign a written informed consent.
• Patient is ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Patient must have surgical consult to verify patient is a surgical candidate within 28 days prior to enrollment.
• Patient must have resectable primary PDAC based on contrast-enhanced CT or MRI of the chest, abdomen, and pelvis performed no more than 4 weeks before enrollment/baseline. Note that if CT or MRI was performed more than 4 weeks before this visit, imaging needs to be repeated to evaluate eligibility in the study. Resectable primary tumor is defined as:
• No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery).

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.