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CAR-T Hepatic Artery Infusions and Sir-Spheres for Liver Metastases (HITM-SIR)

Primary Purpose

Liver Metastases

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

anti-CEA CAR-T cells

Sir-Spheres

About this trial

This is an interventional treatment trial for Liver Metastases focused on measuring Colorectal cancer, Liver metastases, Breast cancer, Gastric cancer, Pancreas cancer, Carcinoembryonic antigen, CAR-T, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Roger Williams Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CEA CAR-T cells + Sir-Spheres

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety of CAR-T cell hepatic artery infusions in combination with Sir-Spheres as Measured by Number of Participants with Adverse Events

To determine the safety and regimen limiting toxicity (RLT) of a standard of care treatment with Yttrium-90 Sir-Spheres Microspheres when following anti-CEA CAR-T hepatic artery infusions (HAI) for CEA-expressing liver metastases.

Secondary Outcome Measures

Treatment response (Liver tumor response by MRI, PET, CEA level, and biopsy)

Liver tumor response by MRI, PET, CEA level, and biopsy RECIST and immune related response criteria (MRI & PET) By evidence of tumor necrosis and fibrosis (biopsy)

Serum cytokine levels

Measurement of cytokines as indicators of immune response

CAR-T detection in liver tumors, normal liver, and extrahepatic sites

Quantification of CAR-T cells in biopsy and blood samples

Full Information

NCT ID

NCT02416466

First Posted

March 30, 2015

Last Updated

March 25, 2019

Sponsor

Roger Williams Medical Center

Collaborators

Sirtex Medical

1. Study Identification

Unique Protocol Identification Number

NCT02416466

Brief Title

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

Acronym

HITM-SIR

Official Title

Phase Ib Trial of CAR-T Hepatic Artery Infusions Followed by Selective Internal Radiation Therapy (SIRT) With Yttrium-90 Sir-Spheres® for CEA-Expressing Liver Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

April 2015 (undefined)

Primary Completion Date

November 21, 2016 (Actual)

Study Completion Date

June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Roger Williams Medical Center

Collaborators

Sirtex Medical

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Metastases

Keywords

Colorectal cancer, Liver metastases, Breast cancer, Gastric cancer, Pancreas cancer, Carcinoembryonic antigen, CAR-T, Immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

anti-CEA CAR-T cells + Sir-Spheres

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

anti-CEA CAR-T cells

Other Intervention Name(s)

Designer T cells

Intervention Description

Gene modified patient T cells.

Intervention Type

Device

Intervention Name(s)

Sir-Spheres

Other Intervention Name(s)

Selective Internal Radiation Therapy (SIRT), Yttrium-90 microspheres

Intervention Description

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).

Primary Outcome Measure Information:

Title

Safety of CAR-T cell hepatic artery infusions in combination with Sir-Spheres as Measured by Number of Participants with Adverse Events

Description

Time Frame

14 weeks

Secondary Outcome Measure Information:

Title

Treatment response (Liver tumor response by MRI, PET, CEA level, and biopsy)

Description

Liver tumor response by MRI, PET, CEA level, and biopsy RECIST and immune related response criteria (MRI & PET) By evidence of tumor necrosis and fibrosis (biopsy)

Time Frame

14 weeks

Title

Serum cytokine levels

Description

Measurement of cytokines as indicators of immune response

Time Frame

14 weeks

Title

CAR-T detection in liver tumors, normal liver, and extrahepatic sites

Description

Quantification of CAR-T cells in biopsy and blood samples

Time Frame

14 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven C Katz, MD

Organizational Affiliation

Roger Williams Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Roger Williams Medical Center

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

02908

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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