Clinical trial NCT02850536: CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer
Official title: Phase Ib Trial of CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions Delivered With the Surefire Infusion System (SIS) for CEA-Expressing Liver Metastases or Pancreas Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Metastases
Keywords: Colorectal Cancer
Liver Metastases
Breast Cancer
Gastric Cancer
Pancreas Cancer
Carcinoembryonic antigen
CAR-T
Immunotherapy
Lead sponsor: Roger Williams Medical Center
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: Sorrento Therapeutics, Inc.
First posted: 2016-08-01
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, fixed dose, phase Ib trial of anti-CEA CAR-T cell infusions delivered via the hepatic artery or splenic vein using the Surefire Infusion System (SIS) for patients with CEA-expressing liver metastases or pancreas cancer.

Detailed description: Patients undergo leukapheresis from which peripheral blood mononuclear cells are purified. T cells are activated and then re-engineered to express chimeric antigen receptors (CARs) specific for CEA. Cells are expanded in culture and returned to the patient by percutaneous hepatic artery infusion at specific cell doses. Prior to the first dose, each patient will undergo diagnostic angiography to verify suitable arterial anatomy. Three anti-CEA CAR-T doses per patient are planned at 1-week intervals. Low dose interleukin-2 will be given via an ambulatory infusion pump for 4 weeks. Normal liver and tumor biopsies will be obtained at the time of the initial diagnostic angiogram and during the final session following the 3rd CAR-T infusion.

Patients with CEA+ liver metastases who exhibit in-liver control following CAR-T therapy who also have CEA+ primary pancreatic tumors may be eligible to receive direct intrapancreatic CAR-T retrograde venous infusions. A maximum of 2 infusions will be delivered. No additional IL-2 will be given and there will be no additional biopsies.

Eligibility criteria: Inclusion Criteria:

* Patient with histologically confirmed diagnosis of CEA+ adenocarcinoma and liver metastases. Patient must have either histologic confirmation of the liver metastases or histologic documentation of the primary tumor and definitive radiologic evidence of liver involvement. Measurable disease is required with lesions of \> 1.0 cm by CT. Soluble CEA is not acceptable as the sole measure of disease. Limited extrahepatic disease is acceptable if confined to the lungs or peritoneal cavity.
* Tumor must be CEA-expressing as demonstrated by elevated serum CEA levels (≥10ng/ml) or immunohistochemistry on a biopsy specimen. Archived tissue is acceptable for determination of CEA expression.
* Patient must be at least 18 years of age.
* Patient able to understand and sign informed consent.
* Patient with a life expectancy of greater than four months.
* Patient failed at least one line of standard systemic chemotherapy and has unresectable disease.
* Patient with performance status of 0 to 1 (ECOG).
* Patient with adequate organ function as defined in protocol.
* Acceptable hepatic vascular anatomy as determined by CT, MR, or conventional angiography. A nuclear medicine study will be performed to document the absence of a significant hepatic-pulmonary shunt (\<20%).

Exclusion Criteria:

* Female patients of childbearing age will be tested for pregnancy. Pregnant patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol on human sperm and the need to practice birth control.
* Patients with serious or unstable renal, hepatic, pulmonary, cardiovascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded, as outlined in section 5.2.8.
* Patients with active clinical disease caused by CMV, hepatitis B or C, HIV or tuberculosis will be excluded from the study.
* Patients who have had cytotoxic and/or radiation therapy within 4 weeks prior to entry into the trial or 4 weeks prior to infusion will be excluded. Patients with other concurrent malignancies will be excluded.
* Patients requiring systemic steroids will be excluded.
* Patients with unsuitable hepatic vascular anatomy will be excluded from the study.
* Patients with extrahepatic metastatic disease beyond the lungs or abdominal/ retroperitoneal lymph nodes.
* Patients with \>50% liver replacement at time of treatment will be excluded.
* Previous external beam radiotherapy to the liver.
* Portal vein thrombosis.

Primary outcomes:
measure: Safety of CAR-T cell hepatic artery infusions delivered using the Surefire Infusion System (SIS) as Measured by Number of Participants with Adverse Events
timeFrame: 10 weeks
Secondary outcomes:
measure: Radiographic treatment response by MRI
timeFrame: 10 weeks
measure: Radiographic treatment response by PET
timeFrame: 10 weeks
measure: CAR-T detection in liver tumors
timeFrame: 10 weeks
measure: CAR-T detection in normal liver tissue
timeFrame: 10 weeks
measure: CAR-T detection in extrahepatic sites
timeFrame: 10 weeks
measure: Serum Cytokine Levels
timeFrame: 10 weeks
measure: CEA level
timeFrame: 10 weeks
measure: Tumor biopsy
timeFrame: 10 weeks
measure: Safety of Direct Intrapancreatic CAR-T Retrograde Venous Infusions (RVI) Delivered Using the Surefire Infusion System (SIS)
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
Study officials:
affiliation: Roger Williams Medical Center
name: Steven C. Katz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Richard Schulick, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Katz SC, Moody AE, Guha P, Hardaway JC, Prince E, LaPorte J, Stancu M, Slansky JE, Jordan KR, Schulick RD, Knight R, Saied A, Armenio V, Junghans RP. HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery. J Immunother Cancer. 2020 Aug;8(2):e001097. doi: 10.1136/jitc-2020-001097.