NCT02416466

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 30, 2015

Completed
2 days until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 15, 2015

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 21, 2016

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

March 26, 2019

Status Verified

March 1, 2019

Enrollment Period

1.6 years

First QC Date

March 30, 2015

Last Update Submit

March 25, 2019

Conditions

Liver Metastases

Keywords

Colorectal cancerLiver metastasesBreast cancerGastric cancerPancreas cancerCarcinoembryonic antigenCAR-TImmunotherapy

Outcome Measures

Primary Outcomes (1)

  • 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.

    14 weeks

Secondary Outcomes (3)

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

    14 weeks

  • Serum cytokine levels

    14 weeks

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

    14 weeks

Study Arms (1)

anti-CEA CAR-T cells + Sir-Spheres

EXPERIMENTAL

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.

Biological: anti-CEA CAR-T cellsDevice: Sir-Spheres

Interventions

anti-CEA CAR-T cellsBIOLOGICAL

Gene modified patient T cells.

Also known as: Designer T cells
anti-CEA CAR-T cells + Sir-Spheres
Sir-SpheresDEVICE

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).

Also known as: Selective Internal Radiation Therapy (SIRT), Yttrium-90 microspheres
anti-CEA CAR-T cells + Sir-Spheres

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Roger Williams Medical Center

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Colorectal NeoplasmsBreast NeoplasmsStomach NeoplasmsPancreatic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesStomach DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System Diseases

Study Officials

  • Steven C Katz, MD

    Roger Williams Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 30, 2015

First Posted

April 15, 2015

Study Start

April 1, 2015

Primary Completion

November 21, 2016

Study Completion

June 1, 2018

Last Updated

March 26, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Locations

US(1)