Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03132792
Other study ID # ADP-0033-001
Secondary ID
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date May 8, 2017
Est. completion date July 7, 2036

Study information

Verified date August 2022
Source Adaptimmune
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This first time in human study is intended for men and women between 18 and 75 years of age who have advanced liver cancer which has grown or returned after being treated or another AFP expressing tumor. 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 or other AFP expressing tumor types. This study is for subjects who have a blood test positive for appropriate HLA-A*02 P Group and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein (Liver only). 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 45
Est. completion date July 7, 2036
Est. primary completion date July 7, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Key Inclusion Criteria: 1. Subject is = 18 years and = 75 years of age and has voluntarily agreed to participate by giving written informed consent in accordance with ICH GCP Guidelines and applicable local regulations. 2. Histologically confirmed HCC, not amenable to transplant, resection. Subjects may undergo loco-regional therapy after enrollment but not at time of lymphodepletion. Or Histologically confirmed diagnosis of another AFP expressing tumor (e.g. cholangiocarcinoma). 3. Measurable disease according to RECIST 1.1 criteria prior to lymphodepletion. 4. Progressive disease following or intolerant of or refuses standard of care systemic therapy prior to lymphodepletion. 5. Positive for any A*02:01 P group allele. 6. a) Group 1, 2, 3, (HCC) 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 =100ng/mL and their non-cancerous liver tissue has =5% cells stained for AFP at any intensity by immunohistochemistry. 6. b) Group 4 (other AFP expressing tumor types) Subjects will be eligible for enrollment if they meet either one of these AFP expression criteria: o Serum AFP levels of =100ng/mL and their non-cancerous liver tissue (if applicable) has =5% cells stained for AFP at any intensity by immunohistochemistry. 7. Life expectancy of > 4 months 8. Child-Pugh score = 6 9. Eastern Cooperative Oncology Group (ECOG) 0-1 10. 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 P Group, HLA-A*02:03 P group or null alleles or positive for the following alleles: HLA-C*04:04 or HLA-B*51:03. 2. Prior liver transplant 3. Received the following prior to leukapheresis: 1. Cytotoxic chemotherapy, immune therapy and biological therapy within 3 weeks 2. Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled or topical steroids is not exclusionary 3. Sorafenib/Regorafenib/Lenvatinib within 1 week 4. Cabozantinib within 2 weeks 5. Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune Study Physician. 4. Received the following prior to lymphodepleting chemotherapy : 1. Cytotoxic chemotherapy or loco-regional therapy within 3 weeks, liver directed radiation therapy within three months. 2. Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled or topical steroids is not exclusionary 3. Bone/soft tissue directed palliative radiotherapy within 4 weeks. 4. Investigational treatment or clinical trial within 4 weeks. 5. Sorafenib/Regorafenib/Lenvatinib within 1 week. 6. Cabozantinib within 2 weeks 7. Prior cancer-directed immunotherapy within 4 weeks, including monoclonal antibodies against PD-1 receptor or ligand. 8. Use of an experimental vaccine within 2 months in the absence of tumor response. The subject should be excluded if their disease is responding to an experimental vaccine given within 6 months 9. Any previous gene therapy using an integrated vector 10. Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune Study Physician. 5. Toxicity persisting from previous anti-cancer therapy of = Grade 2 (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g. peripheral neuropathy) can be enrolled on a case-by-case basis with prior consultation and agreement with the Sponsor Study Physician. 6. Major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities. 7. Bleeding = Grade 2 in the past 3 months prior to lymphodepletion 8. Therapeutic anticoagulation from lymphodepletion until platelet count recovery (prophylactic heparin allowed) 9. Clinically or radiographically detectable ascites (beyond trace/rim of ascites) or ascites requiring medication 10. Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring medication 11. Active viral hepatitis Subjects positive for hepatitis B surface antigen not on antiviral treatment/prophylaxis or subjects with detectable hepatitis B DNA 1. Subjects with resolved (surface antigen negative, core antibody positive) or chronic stable (surface antigen positive) hepatitis B on antiviral treatment/prophylaxis with DNA levels of =100 IU/mL are allowed with HBV DNA monitoring after treatment 2. Subjects with hepatitis C allowed provided they meet all other eligibility criteria 12. Positive serology for HIV 13. Positive serology for HTLV 1 or 2 14. History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. Subjects with history of idiopathic autoimmune hepatitis are excluded. Subjects who experienced hepatitis during treatment with check point inhibiting antibodies are not excluded. 15. Subject has brain metastases. 16. Other active malignancy besides HCC or other eligible AFP expressing tumor types within 3 years. 17. Electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing a QTc interval =450 msec in males and =470 msec in females (=480 msec for subjects with Bundle Branch Block (BBB) over consecutive ECGs). 18. Bacterial or opportunistic infection within 3 months of treatment (upper respiratory infection and uncomplicated urinary tract infection allowed) 19. Uncontrolled intercurrent illness considered by the Investigator to add appreciable risk to study participation, including but not limited to: 1. Clinically significant cardiac disease defined by CHF New York Heart Association (NYHA) > Class 1; uncontrolled clinically significant arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or myocardial infarction) in last 6 months. 2. Oxygen dependent lung disease. 3. Clinically significant psychiatric illness/social situations that would limit compliance with study requirements. 4. History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) in last 6 months. 20. Pregnant or breastfeeding 21. Alcohol or illicit drug dependency 22. Known contraindication to cyclophosphamide, fludarabine, mesna, G-CSF or other agents associated with study treatment.

Study Design


Intervention

Genetic:
Autologous genetically modified AFP?³³²T cells
Infusion of autologous genetically modified AFP?³³²T cells

Locations

Country Name City State
France Paoli Calmettes Institute Marseille Cedex
France Centre Eugène Marquis Rennes
France Institute Gustave Roussy Villejuif
Spain University Hospital of Barcelona Barcelona
Spain University Hospital of Navarra Pamplona
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom Guy's Hospital London
United Kingdom NIHR UCLH Clinical Research London
United Kingdom The Christie NHS Foundation Trust Manchester
United States Winship Cancer Institute - Emory University Atlanta Georgia
United States University of Maryland, Greenebaum Cancer Center Baltimore Maryland
United States Massachusetts General Hospital Boston Massachusetts
United States MD Anderson Cancer Center Houston Texas
United States UCLA Los Angeles California
United States USC/Norris Comprehensive Cancer Center Los Angeles California
United States University of Miami Miami Florida
United States Mayo Clinic Arizona Phoenix Arizona
United States Mayo Clinic Clinical Trial Referral Office Rochester Minnesota
United States Washington University - School of Medicine Saint Louis Missouri
United States Fred Hutchinson Cancer Research Centre Seattle Washington
United States SCCA Immunotherapy Trials Intake Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  France,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of subjects with dose-limiting toxicity (DLT) and adverse events (AEs) and determination of optimally tolerated dose range, including serious adverse events (SAE). Determine if treatment with autologous genetically modified T cells, (AFP?³³²T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments including chemistry, hematology, coagulation, cardiac assessments including ECG, and cardiac Troponin 2 years
Secondary Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1 2 years
Secondary Interval between the date of first T cell infusion dose and first documented evidence of CR or PR Evaluation of the efficacy of the treatment by assessment of time to first response 2 years
Secondary Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause Evaluation of the efficacy of the treatment by assessment of duration of response 2 years
Secondary Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause Evaluation of the efficacy of the treatment by assessment of duration of stable disease 2 years
Secondary Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause Evaluation of the efficacy of the treatment by assessment of progression-free survival 2 years
Secondary Interval between the date of first T cell infusion and date of disease progression or death due to any cause Evaluation of the efficacy of the treatment by assessment of overall survival 2 years
See also
  Status Clinical Trial Phase
Recruiting NCT03971201 - A Randomized Phase II Trial of Surgery Plus Sorafenib vs. Sorafenib Alone for Hepatocellular Cancer (HCC) With Portal Vein Invasion Phase 2
Recruiting NCT05489250 - The PLATON Network
Recruiting NCT04484636 - PLATON - Platform for Analyzing Targetable Tumor Mutations (Pilot-study) N/A
Completed NCT01967823 - T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer Phase 2
Terminated NCT00878215 - Clinical Application of Image-Guided Liver Surgery Phase 2
Completed NCT04212286 - Comparing the Diagnostic Efficiencies of CEUS and EOB-MRI in Patients With High Risk of HCC N/A
Recruiting NCT05992220 - Atezolizumab Plus Bevacizumab Alone or Combined With External Beam Radiotherapy for HCC With Macrovascular Invasion Phase 2
Completed NCT02073435 - A2ALL-Patients Safety System Improvements in Living Donor Liver Transplantation
Active, not recruiting NCT01522937 - A Study of Individualized Stereotactic Body Radiation Therapy (SBRT) for Intrahepatic Cancer Phase 2
Terminated NCT05061537 - Study of PF-07263689 in Participants With Selected Advanced Solid Tumors Phase 1
Active, not recruiting NCT04166240 - Measuring and Improving the Safety of Test Result Follow-Up N/A
Withdrawn NCT02288507 - Sorafenib Concurrent With Yttrium-90 Transarterial Radioembolization in Patients With Advanced Hepatocellular Cancer Phase 1
Terminated NCT03026803 - A Study of Oxaliplatin and Capecitabine in Unresectable Metastatic Hepatocellular Cancer Phase 2
Active, not recruiting NCT04682847 - Radiotherapy With Iron Oxide Nanoparticles (SPION) on MR-Linac for Primary & Metastatic Hepatic Cancers
Active, not recruiting NCT05100082 - Survey of Cabozantinib Tablets Used To Treat People With Hepatocellular Carcinoma
Active, not recruiting NCT03195699 - Oral STAT3 Inhibitor, TTI-101, in Patients With Advanced Cancers Phase 1
Completed NCT02616692 - HCC Patient Preferences in Japan N/A
Recruiting NCT01849588 - Sorafenib for Hepatocellular Cancer With Chronic Hepatitis C Phase 4
Suspended NCT00909558 - Safety and Effectiveness Study of Autologous Natural Killer and Natural Killer T Cells on Cancer Phase 1
Completed NCT00997022 - Trial of Sorafenib in Hepatocellular Cancer (HCC) Transplant Patients Phase 1