Clinical trial NCT03818165: Phase 1b Study of CAR2Anti-CEA CAR-T Cell Hepatic Infusions for Pancreatic Carcinoma Patients With CEA+ Liver Metastases
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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Pancreatic Carcinoma
Keywords: pancreatic carcinoma
Cacinomaembryonic antigen postive (CEA +)
liver metastases
pancreatic cancer
CEA
metastatic pancreatic carcinoma
metastatic pancreatic cancer
phase 1
Lead sponsor: Sorrento Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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%.

Primary outcomes:
measure: Assess preliminary efficacy by overall survival
timeFrame: 6 months
Secondary outcomes:
measure: Assess preliminary efficacy by radiographic response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: 6 months
measure: Assess preliminary efficacy by metabolic response rate using PET Response Criteria in Solid Tumors (PERCIST)
timeFrame: 6 months
measure: Assess preliminary efficacy by response rate using Immune-related Response Criteria (irRC)
timeFrame: 6 months
measure: Assess preliminary efficacy by histologic response rate using pathologic response in biopsy specimens
timeFrame: 6 months
measure: Assess preliminary efficacy by serologic response rates by CEA levels
timeFrame: 6 months
measure: Assess preliminary efficacy by serologic response rates by CA 19-9 levels
timeFrame: 6 months
measure: Assess preliminary efficacy by duration of response in accordance with RECIST criteria
timeFrame: 6 months
measure: Assess preliminary efficacy by in-liver progression free survival (PFS)
timeFrame: 6 months
Other outcomes:
measure: Assess if serum cytokine levels correlate with response and/or toxicity to hepatic arterial infusions.
timeFrame: 6 months
measure: Assess if neutrophil:lymphocyte ratios correlate with response
timeFrame: 6 months
measure: Assess the persistence of CAR-T cells circulating in blood over time
timeFrame: 6 months
measure: Assess the persistence of CAR-T cells in liver tumor biopsies over time
timeFrame: 6 months
measure: Assess if circulating tumor cells (CTC) correlate with response
timeFrame: 6 months
Locations:
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
Study officials:
affiliation: Roger Williams Medical Center
name: Steven C Katz, MD
role: PRINCIPAL_INVESTIGATOR
References: