Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03818165
Recruitment Status : Active, not recruiting
First Posted : January 28, 2019
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Sorrento Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Carcinoma Biological: CAR2 Anti-CEA CAR-T cells Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Three doses of CAR2 Anti-CEA CAR T Cells 1 x 10e10 cells by hepatic artery infusion (on Days 1, 8, and 15) of each 28-day cycle in the Treatment Period using the HITM method and Surefire device, with IL-2 systemic infusion. Patient may receive up to three 28-day cycles of CAR-T therapy in the Treatment Period.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2022

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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. 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.

  7. 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.

  8. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03818165


Locations
Layout table for location information
United States, Rhode Island
Roger Williams Medical Center
Providence, Rhode Island, United States, 02908
Sponsors and Collaborators
Sorrento Therapeutics, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Steven C Katz, MD Roger Williams Medical Center
Layout table for additonal information
Responsible Party: Sorrento Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03818165    
Other Study ID Numbers: SOR-CART-CEA-001
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sorrento Therapeutics, Inc.:
pancreatic carcinoma
Cacinomaembryonic antigen postive (CEA +)
liver metastases
pancreatic cancer
CEA
metastatic pancreatic carcinoma
metastatic pancreatic cancer
phase 1
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Neoplasm Metastasis
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases