Malignant Tumor of Pancreas Metastatic to Liver Clinical Trial
Official title:
A Randomized Open-Label Phase 2b Study of Hepatic Infusions of Anti-CEA CAR-T Cells Alternating With Systemic Chemotherapy Versus Chemotherapy Alone In Patients With Liver Metastases Due To CEA-Expressing Pancreatic Adenocarcinoma
This study is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy alone in patients with CEA-expressing pancreatic adenocarcinoma with liver metastases.
The study consists of 5 periods: Screening/Leukapheresis Period, Bridging Therapy Period, Randomization Period, Treatment Period, and Observation Period (which will be the long-term follow-up period to monitor for overall survival and long-term safety). Patients in this trial with CEA-expressing pancreatic adenocarcinoma with liver metastases must have developed disease progression after first-line treatment with FOLFIRINOX (irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin) or gemcitabine-based chemotherapy. Patients will be randomized to either the "anti-CEA CAR-T Cells + systemic chemotherapy treatment arms", or the "chemotherapy alone treatment arms." If the patients achieve at least stable disease during the Bridging Therapy Period, they will be in the Second-Line Group of Treatment Arms. Patients who develop disease progression during the Bridging Period will be in the Third-Line Group of Treatment Arms. Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms of "Anti-CEA CAR-T cells plus systemic chemotherapy" will receive hepatic infusions of Anti-CEA CAR-T cells in Cycles 1 and 3 (ie, each 42-day cycle is 3 weekly doses of Anti-CEA CAR-T cells administered as hepatic arterial infusions using a PEDD device with low dose systemic IL-2 support), alternating with the systemic chemotherapy regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles >= 4. Systemic chemotherapy will be administered in 28-day cycles until the development of disease progression. Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms "chemotherapy alone" arms will continue to receive the same systemic chemotherapy that they received during the Bridging Therapy Period. Systemic chemotherapy will be administered in 28-day or 21-day cycles (depending on the type of systemic chemotherapy regimen the patient will receive) until the development of disease progression. ;