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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
doses will be delivered by hepatic arterial infusions using pressure enhanced delivery device (PEDD)
Roger Williams Medical Center
Providence, Rhode Island, United States
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.
Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: 6 months
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.
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Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: 6 months