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

Liver Metastases Clinical Trial

— HITM-SURE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02850536
• Other study ID #: 350-74
• Status: Completed
• Phase: Phase 1
• Start date: February 1, 2017
• Est. completion date: September 17, 2021

Study information

• Verified date: October 2021
• Source: Roger Williams Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: September 17, 2021
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Pancreatic Neoplasms

Intervention

Biological:
• anti-CEA CAR-T cells
Gene modified patient T cells

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado
United States	Roger Williams Medical Center	Providence	Rhode Island

Sponsors (3)

Lead Sponsor	Collaborator
Roger Williams Medical Center	Sorrento Therapeutics, Inc., University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Radiographic treatment response by MRI	Changes in tumor size	10 weeks
Secondary	Radiographic treatment response by PET	Changes in tumor metabolic activity	10 weeks
Secondary	CAR-T detection in liver tumors	Quantification of CAR-T cells in liver tumor core biopsies	10 weeks
Secondary	CAR-T detection in normal liver tissue	Quantification of CAR-T cells in normal liver core biopsies	10 weeks
Secondary	CAR-T detection in extrahepatic sites	Quantification of CAR-T in blood samples	10 weeks
Secondary	Serum Cytokine Levels	Measurement of cytokines as indicators of immune response	10 weeks
Secondary	CEA level	Measurement of serum tumor marker (ng/ml)	10 weeks
Secondary	Tumor biopsy	Assessment of tumor necrosis and fibrosis	10 weeks
Secondary	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