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AFPᶜ³³²T in Advanced HCC

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ClinicalTrials.gov Identifier: NCT03132792
Recruitment Status : Recruiting
First Posted : April 28, 2017
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

Brief Summary:

This first time in human study is intended for men and women at least 18 years of age who have advanced liver cancer which has grown or returned after being treated. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer. This study is for subjects who have a blood test positive for appropriate HLA-A*02 and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein.

The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.

The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.

Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.


Condition or disease Intervention/treatment Phase
Hepatocellular Cancer Genetic: Autologous genetically modified AFPᶜ³³²T cells Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFPᶜ³³²T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC)
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Autologous genetically modified AFPᶜ³³²T cells Genetic: Autologous genetically modified AFPᶜ³³²T cells
Infusion of autologous genetically modified AFPᶜ³³²T cells




Primary Outcome Measures :
  1. Number of subjects with dose-limiting toxicity (DLT) and adverse events (AEs) and determination of optimally tolerated dose range, including serious adverse events (SAE). [ Time Frame: 2 years ]
    Determine if treatment with autologous genetically modified T cells, (AFPᶜ³³²T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments including chemistry, hematology, coagulation, cardiac assessments including ECG, and cardiac Troponin


Secondary Outcome Measures :
  1. Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1

  2. Interval between the date of first T cell infusion dose and first documented evidence of CR or PR [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of time to first response

  3. Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of response

  4. Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of stable disease

  5. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of progression-free survival

  6. Interval between the date of first T cell infusion and date of disease progression or death due to any cause [ Time Frame: 2 years ]
    Evaluation of the efficacy of the treatment by assessment of overall survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Histologically confirmed HCC, not amenable to transplant, resection. Subjects may undergo loco-regional therapy after enrollment but not at time of lymphodepletion.
  2. Measurable disease according to RECIST 1.1 criteria prior to lymphodepletion.
  3. Progressive disease following or intolerant of or refuses standard of care systemic therapy prior to lymphodepletion.
  4. Positive for HLA-A*02:01or HLA-A*02:642 allele.
  5. Subjects will be eligible for enrollment if they meet either one of these AFP expression criteria:

    • AFP expression of ≥1+ in ≥20% of tumor cells by immunohistochemistry and their non-cancerous liver tissue has ≤5% cells stained for AFP at any intensity by immunohistochemistry.
    • Serum AFP levels of ≥400ng/mL and their non-cancerous liver tissue has ≤5% cells stained for AFP at any intensity by immunohistochemistry.
  6. Life expectancy of > 4 months
  7. Child-Pugh score ≤ 6
  8. Eastern Cooperative Oncology Group (ECOG) 0-1
  9. Subject must have adequate organ function as defined in the protocol.

Key Exclusion Criteria:

  1. Positive for any of the HLA-A*02 allele other than HLA-A*02:01 or HLA-A*02:642 (except null alleles or HLA-A*02:03) or the following alleles: HLA-C*04:04 or HLA-B*51:03.
  2. Prior liver transplant
  3. Clinically or radiographically detectable ascites (beyond trace/rim of ascites) or ascites requiring medication
  4. Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring medication
  5. Subject has brain metastases.
  6. Other active malignancy besides HCC within 3 years.

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): NCT03132792


Locations
United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Ramona Lujan, RN    323-409-4366    Lujan_R@med.usc.edu   
Contact: Raluca Agafitei       Raluca.Agafitei@med.usc.edu   
Principal Investigator: Anthony B El-Khoueiry, MD         
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Anna Crosetti    310-825-2903    ACrosetti@mednet.ucla.edu   
Contact: Alice Polyakov, BS    310-829-5471    apolyakov@mednet.ucla.edu   
Principal Investigator: Richard S Finn, MD         
University of California, San Francisco Withdrawn
San Francisco, California, United States, 94143
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Weiwan Wang    305-243-2122    wwang1@med.miami.edu   
Contact: Nathalie Luis    305-243-7648    nluis@med.miami.edu   
Principal Investigator: Lynn Feun, MD         
United States, Maryland
University of Maryland, Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Cheryl A Young, BSN    410-328-8611    cheryl.young@umm.edu   
Contact: Navid Saeidi       Navid.saeidi@umm.edu   
Principal Investigator: Peter H Hausner, MD, PhD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kevin Lindell    617-726-3914    klindell@mgh.harvard.edu   
Principal Investigator: Lipika Goyal, MD         
United States, Minnesota
Mayo Clinic Clinical Trial Referral Office Recruiting
Rochester, Minnesota, United States, 55905
Contact: Referral Office    855-776-0015      
Principal Investigator: Amit Mahipal, MBBS         
United States, Washington
SCCA Immunotherapy Trials Intake Recruiting
Seattle, Washington, United States, 98109
Contact: Trials Intake    206-606-4668    immunotherapy@seattlecca.org   
Principal Investigator: Kaylyn K Man Wong, MD         
Spain
University Hospital of Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Neus LLarch    34 93 227 5400 ext 3303    NLLARCH@clinic.cat   
Contact: Margada Quintas       mquintas@clinic.cat   
Principal Investigator: Jordi Bruix, MD         
University Hospital of Navarra Recruiting
Pamplona, Spain, 31008
Contact: Carmen Fuertes    34 948 296 637    cfuertes@unav.es   
Contact: Amaya Redin         
Principal Investigator: Bruno Sangro, MD         
United Kingdom
NIHR UCLH Clinical Research Recruiting
London, United Kingdom, W1T7HA
Contact: Adoracion Jayme, RN    02034472929    adoracion.jayme@nhs.net   
Contact: Marivic Ricamara       marivic.ricamara@nhs.net   
Principal Investigator: Tim Meyer, MBBS, PhD, FRCP         
Sponsors and Collaborators
Adaptimmune
Investigators
Principal Investigator: Richard S Finn, MD University of California, Los Angeles

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT03132792     History of Changes
Other Study ID Numbers: ADP-0033-001
First Posted: April 28, 2017    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adaptimmune:
Alpha-fetoprotein
Cell Therapy
T Cell Therapy
SPEAR T Cell
Immuno-oncology
Metastatic
Previously treated
T Cell Receptor

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type