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

Primary Purpose

Metastatic Pancreatic Carcinoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CAR2 Anti-CEA CAR-T cells
Sponsored by
Sorrento Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Carcinoma focused on measuring pancreatic carcinoma, Cacinomaembryonic antigen postive (CEA +), liver metastases, pancreatic cancer, CEA, metastatic pancreatic carcinoma, metastatic pancreatic cancer, phase 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%.

Sites / Locations

  • Roger Williams Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR2 Anti-CEA CAR-T cell

Arm Description

3 doses of CAR2 Anti-CEA CAR-T cells for each cycle; up to 3 additional cycles received per investigator discretion

Outcomes

Primary Outcome Measures

Assess preliminary efficacy by overall survival
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

Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)
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.
Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)
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.
Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens
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.
Assess preliminary efficacy by serologic response rates by CEA levels
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.
Assess preliminary efficacy by serologic response rates by CA 19-9 levels
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.
Assess preliminary efficacy by duration of response in accordance with RECIST criteria
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.
Assess preliminary efficacy by in-liver progression free survival (PFS)
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.

Full Information

First Posted
January 23, 2019
Last Updated
January 12, 2023
Sponsor
Sorrento Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03818165
Brief Title
Phase 1b Study of CAR2Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases
Acronym
AntiCEA_CART
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Limited enrollment.
Study Start Date
July 29, 2019 (Actual)
Primary Completion Date
January 19, 2020 (Actual)
Study Completion Date
May 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sorrento Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Carcinoma
Keywords
pancreatic carcinoma, Cacinomaembryonic antigen postive (CEA +), liver metastases, pancreatic cancer, CEA, metastatic pancreatic carcinoma, metastatic pancreatic cancer, phase 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAR2 Anti-CEA CAR-T cell
Arm Type
Experimental
Arm Description
3 doses of CAR2 Anti-CEA CAR-T cells for each cycle; up to 3 additional cycles received per investigator discretion
Intervention Type
Biological
Intervention Name(s)
CAR2 Anti-CEA CAR-T cells
Other Intervention Name(s)
Surefire Precision Infusion System, K171355
Intervention Description
doses will be delivered by hepatic arterial infusions using pressure enhanced delivery device (PEDD)
Primary Outcome Measure Information:
Title
Assess preliminary efficacy by overall survival
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by serologic response rates by CEA levels
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by serologic response rates by CA 19-9 levels
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by duration of response in accordance with RECIST criteria
Description
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.
Time Frame
6 months
Title
Assess preliminary efficacy by in-liver progression free survival (PFS)
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions.
Description
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.
Time Frame
6 months
Title
Assess if neutrophil:lymphocyte ratios correlate with response
Description
As an exploratory analysis, neutrophil:lymphcyte ratios will be calculated to determine if they correlate with response and/or toxicity.
Time Frame
6 months
Title
Assess the persistence of CAR-T cells circulating in blood over time
Description
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.
Time Frame
6 months
Title
Assess the persistence of CAR-T cells in liver tumor biopsies over time
Description
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.
Time Frame
6 months
Title
Assess if circulating tumor cells (CTC) correlate with response
Description
As an exploratory analysis, levels of circulating tumor cells (CTC) will be determined to investigate if decreases in CTC levels correlate with response.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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%.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven C Katz, MD
Organizational Affiliation
Roger Williams Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roger Williams Medical Center
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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