Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03323944
Previous Study | Return to List | Next Study

CAR T Cell Immunotherapy for Pancreatic Cancer

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: NCT03323944
Recruitment Status : Active, not recruiting
First Posted : October 27, 2017
Last Update Posted : August 4, 2021
Sponsor:
Collaborators:
Stand Up To Cancer
Lustgarten
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
Phase I study to establish the safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells in patients with histologically confirmed unresectable or metastatic pancreatic adenocarcinoma

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Cancer of the Pancreas Biological: huCART-meso cells Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Human Chimeric Antigen Receptor Modified T Cells (CAR T Cells) in Patients With Pancreatic Cancer
Actual Study Start Date : September 15, 2017
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: huCART-meso cells via intravenous infusion (IV).
Subjects will receive a single dose of 1-3x10^7/m^2 lentiviral transduced huCART-meso cells on day 0 via intravenous infusion.
Biological: huCART-meso cells
Intravenous administration or local delivery of lentiviral transduced huCART-meso cells.

Experimental: Cohort -1: low dose huCART-meso cells via intravenous infusion
In the event that 2 DLTs occur among subjects enrolled in Cohort 1, then enrollment in Cohort 1 will be stopped and the dose will be de-escalated by 10-fold to 1-3x10^6 cells/m2. Subjects will receive a single dose of 1-3x10^6 cells/m^2 lentiviral transduced huCART-meso cells on day 0.
Biological: huCART-meso cells
Intravenous administration or local delivery of lentiviral transduced huCART-meso cells.

Experimental: Cohort 2 - huCART meso cells via intraperitoneal infusion (IP)
Eligible subjects will receive a single dose of 1-3x107/m2 lentiviral transduced huCART-meso cells on day 0 via intraperitoneal (i.p.) administration. The initial i.p. infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart.
Biological: huCART-meso cells
Intravenous administration or local delivery of lentiviral transduced huCART-meso cells.

Experimental: Cohort 3 - huCART meso cells via intrahepatic infusion (hepatic arterial infusion)
Eligible subjects will receive a single dose of 1-3x107/m2 lentiviral transduced huCART-meso cells on day 0 via intrahepatic delivery (Hepatic Arterial Infusion). The initial intrahepatic infusion may be followed by up to two additional infusions of huCART-meso cells via intravenous (IV) administration at the same dose level, given between 21-42 days apart.
Biological: huCART-meso cells
Intravenous administration or local delivery of lentiviral transduced huCART-meso cells.




Primary Outcome Measures :
  1. Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria [ Time Frame: Day 28, Month 3, Month 6 ]
  2. Progression-free survival (PFS) [ Time Frame: 2 years ]
  3. Overall survival (OS) [ Time Frame: 2 years ]


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

    1. Patients with the following diagnoses:

      1. Cohorts 1 and -1: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma
      2. Cohort 2: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; and either cytologically-proven ascites or known peritoneal disease on radiologic imaging.
      3. Cohort 3: Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma with liver metastases as confirmed by pathology or radiographic imaging.
    2. INCLUSION CRITERIA HAS BEEN RETIRED
    3. Failure of at least one prior standard of care chemotherapy for advanced stage disease.
    4. Subjects must have measurable disease as defined by RECIST 1.1 criteria.
    5. Patients ≥ 18 years of age.
    6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    7. Satisfactory organ and bone marrow function as defined by the following:

      i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 8 g/dL iv. Bilirubin ≤ 2.0x the institutional normal upper limit v. Creatinine ≤ 1.5x the institutional normal upper limit vi. Albumin ≥ 2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5x the institutional normal upper limit viii. Cardiac ejection fraction of ≥40% as measured by resting echocardiogram, with no clinically significant pericardial effusion.

    8. Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
    9. Provides written informed consent.
    10. Subjects of reproductive potential must agree to use acceptable birth control methods
  • Exclusion Criteria:

    1. EXCLUSION CRITERIA HAS BEEN RETIRED
    2. Active invasive cancer other than pancreatic adenocarcinoma. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer, or prostate cancer with PSA level < 1.0) are not excluded.
    3. HIV infection
    4. Active hepatitis B or hepatitis C infection
    5. Active autoimmune disease (including but not limited to: systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation by physician-investigator, with the exception of thyroid replacement.
    6. Patients with ongoing or active infection.
    7. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions or adrenal insufficiency.
    8. Patients requiring supplemental oxygen therapy.
    9. Prior therapy with lentiviral gene modified cells.
    10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
    11. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 3) or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected.
    12. Any clinically significant pleural or peritoneal effusion that cannot be drained with standard approaches. An indwelling drainage device placed prior to eligibility confirmation by physician-investigator is acceptable.
    13. Pregnant or breastfeeding women.
    14. EXCLUSION CRITERIA HAS BEEN RETIRED
    15. Treatment with a PD-1 or PD-L1 inhibitor, including but not limited to nivolumab, pembrolizumab, atezolizumab, and/or durvalumab, within 2 months prior to eligibility confirmation by investigator.
    16. Patients with significant lung disease as follows:
    1. Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.
    2. Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
    3. Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc) 17. Cohort 3 Subjects Only: Patients with a contraindication to IV contrast.

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): NCT03323944


Locations
Layout table for location information
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Stand Up To Cancer
Lustgarten
Investigators
Layout table for investigator information
Principal Investigator: Mark O'Hara, MD Assistant Professor of Medicine, Penn Medicine
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03323944    
Other Study ID Numbers: 827644 (UPCC 14217)
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: August 4, 2021
Last Verified: August 2021

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 University of Pennsylvania:
metastatic adenocarcinoma, pancreas
Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases