Clinical Trials /

CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC)

NCT03682744

Description:

This is an open-label, dose-escalation, phase I trial of the safety and efficacy of anti-CEA intraperitoneal CAR-T infusions for treatment in patients with CEA-expressing adenocarcinoma peritoneal metastases or malignant ascites.

Related Conditions:
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC)
  • Official Title: Immunotherapy for Peritoneal Carcinomatosis (IPC) - A Phase I Study of the Safety and Efficacy of Anti-CEA CAR-T Cell Intraperitoneal Infusions for Treatment of CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites

Clinical Trial IDs

  • ORG STUDY ID: 340-74
  • NCT ID: NCT03682744

Conditions

  • Peritoneal Carcinomatosis
  • Peritoneal Metastases
  • Colorectal Cancer
  • Gastric Cancer
  • Breast Cancer
  • Pancreas Cancer
  • Carcinoembryonic Antigen

Interventions

DrugSynonymsArms
anti-CEA CAR-T cellsGene modified patient T cells, Designer T cellsanti-CEA CAR-T cells

Purpose

This is an open-label, dose-escalation, phase I trial of the safety and efficacy of anti-CEA intraperitoneal CAR-T infusions for treatment in patients with CEA-expressing adenocarcinoma peritoneal metastases or malignant ascites.

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
      intraperitoneal infusion at specific cell doses. One anti-CEA CAR-T dose per patient is
      planned. Additional cycles may be administered at the discretion of the principal
      investigator. Normal peritoneal and tumor biopsies will be obtained at the time of the CAR-T
      infusion, on the final day of the treatment period, and during reporting interval #3.
    

Trial Arms

NameTypeDescriptionInterventions
anti-CEA CAR-T cellsExperimentalOne intraperitoneal infusion of gene-modified anti-CEA T cells are administered to patients with CEA-expressing peritoneal metastases or malignant ascites

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Age ≥ 18 years.
    
              2. Must have documented CEA+ carcinomatosis or malignant ascites as demonstrated by an
                 elevated serum CEA level (≥ 10 ng/mL) or immunohistochemistry on a biopsy or cytologic
                 specimen (archived tissue is acceptable), for determination of CEA expression. Primary
                 tumor may be intact and limited liver and/or lung disease permitted.
    
              3. Must have at least evaluable disease by physical examination, serum tumor markers,
                 radiologic assessment, tumor markers, or laparoscopic visual assessment.
    
              4. Have a life-expectancy ≥ 12 weeks and ECOG performance status ≤ 2.
    
              5. May have low volume of liver metastases defined as < 50% replacement of the liver
                 volume by metastatic disease, as long as all other eligibility criteria are satisfied.
    
              6. Be willing and able to comply with the study schedule and all other protocol
                 requirements.
    
            Exclusion Criteria:
    
              1. 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.
    
              2. Received an investigational study drug within 14 days of leukapheresis or 28 days
                 before receiving first dose of study drug. Exceptions may be granted with medical
                 monitor approval.
    
              3. Received any approved anticancer medication within 14 days of leukapheresis or 14 days
                 before receiving the first dose of study drug. Exceptions may be granted with medical
                 monitor approval.
    
              4. Have any unresolved toxicity > Grade 2 from previous anticancer therapy, except for
                 stable chronic toxicities (≤ Grade 3) that are not expected to resolve.
    
              5. Have a history of histologically confirmed metastases outside the peritoneal cavity,
                 lungs, or liver.
    
              6. Have high volume lung or liver metastases, defined as >5 lung lesions greater than 1
                 cm in size or ≥ 50% replacement the liver volume by metastatic disease.
    
              7. Received CAR-T, CAR-T cell line, CAR-NK, CAR-pNK, or CAR-NK cell line therapies.
    
              8. Have any of the following laboratory results at Screening (Screening volumes must be
                 independent of blood product treatment):
    
                   1. Hemoglobin ≤ 8.0 g/dL
    
                   2. Platelet count < 50 × 109/L
    
                   3. Absolute neutrophil count (ANC) < 1.0 × 109/L
    
              9. Untreated or ongoing intra-abdominal infection or bowel obstruction.
    
             10. Have any of the following laboratory results at Screening, regardless of causality:
    
                   1. Serum creatinine ≥ 3.0, or estimated creatinine clearance ≤ 30 mL/min and not
                      dialysis dependent
    
                   2. Aspartate aminotransferase (AST) ≥ 4 × upper limit of normal (ULN) and total
                      bilirubin ≥ 2.0 mg/dL (except for patients in whom hyperbilirubinemia is
                      attributed to Gilbert's syndrome).
    
             11. Have human immunodeficiency virus (HIV) infection, or hepatitis B virus (HBV) or
                 hepatitis C virus (HCV) viremia, or are at risk for HBV reactivation (at risk for HBV
                 reactivation is defined as being HBsAg positive, or anti-HBc-antibody positive), or
                 are positive for HBV deoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be
                 undetectable by laboratory test.
    
             12. Are pregnant or breastfeeding.
    
             13. Have active bacterial, viral, or fungal infection: patients with ongoing use of
                 prophylactic antibiotics, antiviral agents, or antifungal agents remain eligible as
                 long as there is no evidence of active infection.
    
             14. Has any significant medical condition, laboratory abnormality, or psychiatric illness
                 that would prevent the patient from participating in the study.
    
             15. Has any condition, including the presence of laboratory abnormalities that places the
                 patient at an unacceptable risk if the patient was to participate in the study.
    
             16. Left ventricular ejection fraction (LVEF) < 40%
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:Accepts Healthy Volunteers

    Primary Outcome Measures

    Measure:Safety of Intraperitoneal CAR-T Cell Infusions as Measured by Number of Participants with Adverse Events
    Time Frame:16 weeks
    Safety Issue:
    Description:To determine the safety and maximum tolerated dose (MTD) following intraperitoneal infusion(s) of anti-CEA CAR-T cells for inoperable CEA+ peritoneal metastases or malignant ascites.

    Secondary Outcome Measures

    Measure:Progression-Free Survival
    Time Frame:20 weeks
    Safety Issue:
    Description:As a measure of activity, Progression-free survival (PFS) will be assessed. The events for the assessment of PFS are disease progression and death events
    Measure:Overall Survival
    Time Frame:20 weeks
    Safety Issue:
    Description:As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events.
    Measure:Bowel Obstruction Free Survival
    Time Frame:20 weeks
    Safety Issue:
    Description:Measuring the time frame in which a patient does not experience a bowel obstruction
    Measure:Changes in Quality of Life
    Time Frame:20 weeks
    Safety Issue:
    Description:Changes in quality of life measured by SF-36 pre and post-treatment
    Measure:Response by the Peritoneal Carcinomatosis Index (PCI)
    Time Frame:16 weeks
    Safety Issue:
    Description:Direct visualization of tumor burden assessment by the PCI pre and post-treatment
    Measure:Radiographic treatment response by MRI
    Time Frame:20 weeks
    Safety Issue:
    Description:Changes in tumor size
    Measure:Radiographic treatment response by PET
    Time Frame:20 weeks
    Safety Issue:
    Description:Changes in tumor metabolic activity
    Measure:Serologic response rates
    Time Frame:20 weeks
    Safety Issue:
    Description:Measurement of CEA and CA19-9

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sorrento Therapeutics, Inc.

    Last Updated