CAR-T Hepatic Artery Infusions and Sir-Spheres for Liver Metastases

NCT ID: NCT02416466

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2018-06-30

Brief Summary

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.

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 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.

Conditions

Liver Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anti-CEA CAR-T cells + Sir-Spheres

Three infusions of gene-modified anti-CEA T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach along with low dose IL-2. A single dose of Sir-Spheres will be given 2 weeks following the final T cell dose.

Group Type: EXPERIMENTAL

anti-CEA CAR-T cells

Intervention Type: BIOLOGICAL

Gene modified patient T cells.

Sir-Spheres

Intervention Type: DEVICE

SIR-Spheres microspheres are a medical device used in Selective Internal Radiation Therapy (SIRT) for liver tumors. SIR-Spheres microspheres are a permanent implant and for single use only. The biocompatible resin microspheres containing yttrium-90 have a median diameter of 32.5 microns (range between 20 and 60 microns).

Interventions

anti-CEA CAR-T cells

Gene modified patient T cells.

Intervention Type: BIOLOGICAL

Sir-Spheres

SIR-Spheres microspheres are a medical device used in Selective Internal Radiation Therapy (SIRT) for liver tumors. SIR-Spheres microspheres are a permanent implant and for single use only. The biocompatible resin microspheres containing yttrium-90 have a median diameter of 32.5 microns (range between 20 and 60 microns).

Intervention Type: DEVICE

Other Intervention Names

Designer T cells; Selective Internal Radiation Therapy (SIRT); Yttrium-90 microspheres

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sirtex Medical

INDUSTRY

Sponsor Role: collaborator

Roger Williams Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven C Katz, MD

Role: PRINCIPAL_INVESTIGATOR

Roger Williams Medical Center

Locations

Roger Williams Medical Center

Providence, Rhode Island, United States

Countries

United States

Other Identifiers

383-74

Identifier Type: -

Identifier Source: org_study_id