CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer (HITM-SURE)

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Metastases
• Intervention / Treatment: Biological: anti-CEA CAR-T cells

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: anti-CEA CAR-T cells; Three infusions of gene-modified anti-CEA T cells over the course of 3 weeks into the hepatic artery via a percutaneous approach along with low dose IL-2.	Biological: anti-CEA CAR-T cells; Gene modified patient T cells; Other Names: Designer T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CAR-T cell hepatic artery infusions delivered using the Surefire Infusion System (SIS) as Measured by Number of Participants with Adverse Events	To determine the safety and regimen limiting toxicity (RLT) of anti-CEA CAR-T hepatic artery infusions (HAI) via the Surefire Infusion System (SIS) for CEA-expressing liver metastases	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic treatment response by MRI	Changes in tumor size	10 weeks
Radiographic treatment response by PET	Changes in tumor metabolic activity	10 weeks
CAR-T detection in liver tumors	Quantification of CAR-T cells in liver tumor core biopsies	10 weeks
CAR-T detection in normal liver tissue	Quantification of CAR-T cells in normal liver core biopsies	10 weeks
CAR-T detection in extrahepatic sites	Quantification of CAR-T in blood samples	10 weeks
Serum Cytokine Levels	Measurement of cytokines as indicators of immune response	10 weeks
CEA level	Measurement of serum tumor marker (ng/ml)	10 weeks
Tumor biopsy	Assessment of tumor necrosis and fibrosis	10 weeks
Safety of Direct Intrapancreatic CAR-T Retrograde Venous Infusions (RVI) Delivered Using the Surefire Infusion System (SIS)	RVI via the Surefire Infusion System (SIS) for CEA+ Primary Pancreatic Tumors Following In-liver Disease Control	10 weeks

Collaborators and Investigators

• Sponsor: Roger Williams Medical Center
• Collaborators: University of Colorado, Denver; Sorrento Therapeutics, Inc.
• Investigators: Principal Investigator: Steven C. Katz, MD, Roger Williams Medical Center; Principal Investigator: Richard Schulick, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2017
• Primary Completion (ACTUAL): December 31, 2018
• Study Completion (ACTUAL): September 17, 2021

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 29, 2016
• First Posted (ESTIMATE): August 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer; CAR-T; Immunotherapy; Gastric Cancer; Colorectal Cancer; Pancreas Cancer; Liver Metastases; Carcinoembryonic antigen
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Liver Diseases; Neoplastic Processes; Pancreatic Diseases; Neoplasm Metastasis; Pancreatic Neoplasms; Liver Neoplasms
• Other Study ID Numbers: 350-74

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No