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

Breast Cancer Clinical Trial

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03682744
• Other study ID #: 340-74
• Status: Withdrawn
• Phase: Phase 1
• Start date: September 13, 2018
• Est. completion date: March 2021

Study information

• Verified date: March 2022
• Source: Sorrento Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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%

Related Conditions & MeSH terms

• Adenocarcinoma
• Ascites
• Breast Cancer
• Carcinoembryonic Antigen
• Carcinoma
• Colorectal Cancer
• Gastric Cancer
• Neoplasm Metastasis
• Pancreas Cancer
• Pancreatic Neoplasms
• Peritoneal Carcinomatosis
• Peritoneal Metastases
• Peritoneal Neoplasms

Intervention

Biological:
• anti-CEA CAR-T cells
Intraperitoneal delivery of anti-CEA CAR-T cells

Locations

Country	Name	City	State
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Roger Williams Medical Center	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Sorrento Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of Intraperitoneal CAR-T Cell Infusions as Measured by Number of Participants with Adverse Events	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.	16 weeks
Secondary	Progression-Free Survival	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	20 weeks
Secondary	Overall Survival	As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events.	20 weeks
Secondary	Bowel Obstruction Free Survival	Measuring the time frame in which a patient does not experience a bowel obstruction	20 weeks
Secondary	Changes in Quality of Life	Changes in quality of life measured by Quality of Life Index (IQI) survey pre and post-treatment	20 weeks
Secondary	Response by the Peritoneal Carcinomatosis Index (PCI)	Direct visualization of tumor burden assessment by the PCI pre and post-treatment	16 weeks
Secondary	Radiographic treatment response by MRI	Changes in tumor size	20 weeks
Secondary	Radiographic treatment response by PET	Changes in tumor metabolic activity	20 weeks
Secondary	Serologic response rates	Measurement of CEA and CA19-9	20 weeks