Phase IB/II Study of NRT Combined With Radiotherapy for Advanced HCC (LCRAI-1)

Phase IB/II Study of Personalized New Antigen Reactive Immune Cells (NRT) Combined With Radiotherapy for Advanced Hepatocellular Carcinoma Patients

The study herein successfully developed a new immunotherapeutic approach combined with radiotherapy, and tried to proved it to be more effective and safe.

Study Overview

• Status: Unknown
• Conditions: HCC
• Intervention / Treatment: Biological: NRT; Radiation: Radiotherapy

Detailed Description

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. The resection rate for HCC is approximately 10%-30% and the overall prognosis is very poor with a 5-year survival rate of 5%-6%. The recurrence rate is high after radical resection. In addition to surgery, radiofrequency ablation, transcatheter arterial chemoembolization (TACE), microwave ablation, cryoablation, radioactive seeds implantation, high-intensity-focused ultrasound, radiation therapy, chemotherapy and targeted drugs are available for patients with unresectable tumors; however, the efficacy of these treatments are limited and long-term prognosis in the patients is still poor. Moreover, due to serious side effects induced by treatments such as TACE, chemotherapy and targeted drugs, it may not be possible for patients to continue receiving these therapies. The study herein successfully developed a new immunotherapeutic approach combined with radiotherapy, and tried to proved it to be more effective and safe.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female or male aged 18 years and over, but no more than 75 years;
2. Histologic or cytologic confirmation of advanced hepatocellular carcinoma;
3. Patients with measurable lesions but can not be treated with surgery;
4. Patients with two or over measurable lesions;
5. ECOG≤0-2, Child-pugh A-B;
6. Patients had not received systemic venous chemotherapy ever before;
7. Hematology Index;
8. Neutrophile granulocyte greater than 1.5×10^9/L;
9. Hemoglobin greater than 10g/dL;
10. Platelet greater than 90×10^9/L;
11. Biochemical index
12. Serum bilirubin not greater than 1.5x upper limit of reference range （ULN）
13. ALT or AST not greater than 1.5x ULN
14. Creatinine clearance no less than 60ml/min;
15. Negative pregnancy test for women of childbearing potential;
16. Provision of informed consent;
17. Be able to follow the research program and follow up process;
18. Expected survival time 3 months or more.

Exclusion Criteria:

1. Chemotherapy with experimental drug within 3 months before the start of study therapy;
2. Have at least another primary malignant tumor;
3. Active infection with bacterial or fungal infection;
4. Patients with HIV infection, HCV infection, serious coronary artery disease or asthma, serious cerebrovascular disease or other diseases that the researchers think can not be entered into the group;
5. Women who are pregnant or breast feeding;
6. Drug abuse, clinical or psychological or social factors which will influence the informed. consent or the study implementation;
7. May be allergic to immunotherapy;
8. Radiotherapy and immunotherapy may not be implemented due to social or geographical factors;
9. Weight loss greater 10% within 6 weeks before the start of study therapy;
10. influence the safety or compliance of the patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NRT + radiotherapy; HCC received NRT and radiotherapy	Biological: NRT; Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory. NRTs 0.5~1 x 10^10, will be i.v.Q3 weeks for total 4-6 doses.; Radiation: Radiotherapy; Radiotherapy of the major mass by dose of 5Gy/F * 10F

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events	using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response Rate（RR） will be evaluated according Response Evaluation Criteria	3, 6 and 12 months
Progression free survival (PFS)	the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented	3, 6, 9 and 12 months
Overall Survival (OS)	the duration is measured from the time of treatment to the time of death	At 6, 12 and 18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Th1/Th2 change in the peripheral blood	cytokines are measured by flow cytometry(FCM)	At baseline,and 1 month, 3 months and 6 months
Interferon-gama change of PBMC cells in the peripheral blood stimulated by tumor antigens	Interferon-gama change of PBMC cells by ELISPOT	At baseline,and 1 month, 3 months and 6 months

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Principal Investigator: Baorui Liu, M.D & Ph.D, The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University

Publications and helpful links

General Publications

• Liu C, Shao J, Dong Y, Xu Q, Zou Z, Chen F, Yan J, Liu J, Li S, Liu B, Shen J. Advanced HCC Patient Benefit From Neoantigen Reactive T Cells Based Immunotherapy: A Case Report. Front Immunol. 2021 Jul 13;12:685126. doi: 10.3389/fimmu.2021.685126. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 20, 2017
• Primary Completion (Anticipated): July 20, 2020
• Study Completion (Anticipated): July 20, 2021

Study Registration Dates

• First Submitted: June 18, 2017
• First Submitted That Met QC Criteria: June 24, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2017
• Last Update Submitted That Met QC Criteria: June 24, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: HCC; NRT; TOMO radiotherapy
• Other Study ID Numbers: Nanjing DrumTower Hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No