This is an open label fixed dose phase Ib of anti-CEA CAR-T cells hepatic artery infusions
and yttrium-90 SIR-Spheres in patients with CEA-expressing liver metastases.
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 and one SIR-Sphere dose per patient are planned at 2-week intervals. Low dose
interleukin-2 will be given via an ambulatory infusion pump for 6 weeks.Normal liver and
tumor biopsies will be obtained at the time of the initial diagnostic angiogram and during
the final infusion session.
- 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
- 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%).
- 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.