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

• ClinicalTrials.gov Identifier: NCT02850536
• Recruitment Status: Active, not recruiting
• First Posted: August 1, 2016
• Last Update Posted: October 30, 2020
• Sponsor: Roger Williams Medical Center
• Collaborators: University of Colorado, Denver; Sorrento Therapeutics, Inc.
• Information provided by (Responsible Party): Roger Williams Medical Center

Tracking Information

• First Submitted Date: July 14, 2016
• First Posted Date: August 1, 2016
• Last Update Posted Date: October 30, 2020
• Actual Study Start Date: February 1, 2017
• Actual Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 29, 2016)

Safety of CAR-T cell hepatic artery infusions delivered using the Surefire Infusion System (SIS) as Measured by Number of Participants with Adverse Events [ Time Frame: 10 weeks ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 6, 2018)

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

Original Secondary Outcome Measures (submitted: July 29, 2016)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer
• 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
• Brief 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.

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Liver Metastases

Intervention

Biological: anti-CEA CAR-T cells

Gene modified patient T cells

Other Name: Designer T cells

Study Arms

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.

Intervention: Biological: anti-CEA CAR-T cells

• 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). pii: e001097. doi: 10.1136/jitc-2020-001097.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 29, 2016): 5
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2021
• Actual Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02850536
• Other Study ID Numbers: 350-74
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Roger Williams Medical Center
• Study 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

• PRS Account: Roger Williams Medical Center
• Verification Date: October 2020