Phase 1b Study of CAR2Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases (AntiCEA_CART)

January 12, 2023 updated by: Sorrento Therapeutics, Inc.

Phase 1b Study of the Efficacy and Safety of CAR2 Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases Resistant to Standard Therapy Using the HITM Method and Pressure Enabled Delivery Device

This study is an open-label, single arm phase 1b safety study of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions for pancreatic carcinoma patients with carcinoembryonic antigen positive (CEA+) liver metastases resistant to standard therapy who meet all other eligibility criteria.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Patients will receive weekly 3 doses of CAR2 Anti-CEA CAR-T cells in each 28-day cycle by hepatic arterial infusions using a Pressure Enhanced Delivery Device (PEDD) with low dose systemic IL-2 support. Patients may receive up to 3 cycles of CAR2 Anti-CEA CAR-T cell hepatic arterial infusions, per discretion of the investigator.

All patients who receive investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02908
        • Roger Williams Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have documented CEA+ pancreatic adenocarcinoma liver metastases and have failed greater than or equal to 1 line of conventional systemic therapy.
  • Must have at least evaluable liver metastases.
  • Must have a life-expectancy at least 12 weeks.
  • Patients must be willing and able to comply with the study schedule and all other protocol requirements.
  • Females of childbearing potential must have 2 negative pregnancy tests, agree to pregnancy tests during the study, and sexually active female and male patients must be willing to use an effective birth control method to avoid pregnancy.

Exclusion Criteria:

  • Subjects who have received an investigational study drug within 14 days of leukapheresis or 28 days before receiving first dose of study drug.
  • Subjects who have received any approved anticancer medication within 14 days of leukapheresis or 14 days before receiving the first dose of study drug.
  • Have any unresolved toxicity greater than Grade 2 from previous anticancer therapy.
  • Have a history of confirmed metastases outside the peritoneal cavity, lungs, or liver.
  • More than 50% replacement of one or both liver lobes with tumor.
  • Has tumor causing biliary obstruction not amenable to stenting.
  • Have a high volume of lung or peritoneal metastases.
  • Has received any CAR cell line therapies.
  • Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts at screening.
  • Has untreated or ongoing intra-abdominal infection or bowel obstruction.
  • Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at screening regardless of causality.
  • Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
  • Female patients who are pregnant or breastfeeding.
  • Have active bacterial, viral, or fungal infections.
  • Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent study participation.
  • Left ventricular ejection fraction (LVEF) < 40%.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAR2 Anti-CEA CAR-T cell
3 doses of CAR2 Anti-CEA CAR-T cells for each cycle; up to 3 additional cycles received per investigator discretion
Biological: CAR2 Anti-CEA CAR-T cells
doses will be delivered by hepatic arterial infusions using pressure enhanced delivery device (PEDD)
Other Names:
  • Surefire Precision Infusion System
  • K171355

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess preliminary efficacy by overall survival
Time Frame: 6 months
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by radiographic scans using RECIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by radiographic scans using PERCIST criteria. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by radiographic scans using irRC. Response will be assessed for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by pathologic criteria using biopsies of the liver metastases and measuring necrosis and fibrosis. REsponse rates will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by serologic response rates by CEA levels
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by serologic response rates by CA 19-9 levels
Time Frame: 6 months
As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by duration of response in accordance with RECIST criteria
Time Frame: 6 months
As a measure of activity, duration of response will be measured using radiologic scans and assessed according to RECIST criteria. This will be assess for each patient over a 6-month timeframe during the treatment and observation phases of the protocol.
6 months
Assess preliminary efficacy by in-liver progression free survival (PFS)
Time Frame: 6 months
As a measure of activity, in-liver PFS will be assessed. The events for the assessment of PFS are disease progression and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimate estimates and 95% confidence intervals will be provided where appropriate.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions.
Time Frame: 6 months
As an exploratory analysis, serum cytokine levels will be measured by ELISA to determine if increases in cytokines predict response and/or toxicity to liver arterial infusions.
6 months
Assess if neutrophil:lymphocyte ratios correlate with response
Time Frame: 6 months
As an exploratory analysis, neutrophil:lymphcyte ratios will be calculated to determine if they correlate with response and/or toxicity.
6 months
Assess the persistence of CAR-T cells circulating in blood over time
Time Frame: 6 months
As an exploratory analysis, circulating CAR-T cells will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.
6 months
Assess the persistence of CAR-T cells in liver tumor biopsies over time
Time Frame: 6 months
As an exploratory analysis, the engraftment of CAR-T cells in planned liver tumor biopsies will be analyzed to assess persistence of CAR-T cells during the treatment and observation phases of the study.
6 months
Assess if circulating tumor cells (CTC) correlate with response
Time Frame: 6 months
As an exploratory analysis, levels of circulating tumor cells (CTC) will be determined to investigate if decreases in CTC levels correlate with response.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sorrento Therapeutics, Inc.

Investigators

  • Principal Investigator: Steven C Katz, MD, Roger Williams Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 29, 2019

Primary Completion (Actual)

January 19, 2020

Study Completion (Actual)

May 21, 2021

Study Registration Dates

First Submitted

January 23, 2019

First Submitted That Met QC Criteria

January 23, 2019

First Posted (Actual)

January 28, 2019

Study Record Updates

Last Update Posted (Estimate)

January 16, 2023

Last Update Submitted That Met QC Criteria

January 12, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SOR-CART-CEA-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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