| ISRCTN | ISRCTN11889464 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11889464 |
| EudraCT/CTIS number | 2011-001690-62 |
| Secondary identifying numbers | VERSION 9 : RG_10-148 |
- Submission date
- 28/10/2013
- Registration date
- 11/12/2013
- Last edited
- 06/09/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Prof David Adams
Scientific
Scientific
I-ACT Team
CRCTU, 5th Floor East
Institute of Translational Medicine
Heritage Building
Mindelsohn Way
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| Study design | Phase II randomised trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomised phase II clinical trial of conditioning cyclophosphamide and chemoembolisation with or without vaccination with dendritic cells pulsed with hepg2 lysate in vivo in patients with hepatocellular carcinoma (HCC) |
| Study hypothesis | Current study hypothesis as of 12/02/2019: To determine whether activity due to the addition of dendritic cells (DC) vaccine to chemoembolisation and preconditioning prolongs progression free survival (PFS) and warrants further investigation. Previous study hypothesis: To determine whether activity due to the addition of dendritic cells (DC) vaccine to chemoembolisation and preconditioning cyclophosphamide warrants further investigation in a large randomised phase III clinical trial. |
| Ethics approval(s) | UK National Ethics committee - NRES Committee West Midlands - Coventry and Warwickshire; Ref: 11/WM/0367 |
| Condition | Hepacellular Carcinoma |
| Intervention | Dendritic cell vaccine, Cyclophosphamide, TACE (standard treatment) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Cyclophosphamide |
| Primary outcome measure | Progression Free survival time at every visit |
| Secondary outcome measures | Current secondary outcome measures as of 12/02/2019: 1. Radiological response assessment (RECIST 1.1 criteria) measured at baseline, Day 60 and then every 3 months thereafter 2. Change in the tumour marker serum alpha-fetoprotein (AFP) at every visit 3. Assessment of toxicity using Common Terminology Criteria for Adverse Events (CTCAE) (version 4) at every visit 4. Immune response at every visit 5. Overall survival time 6. Radiological response based on modified RECISIT (mRECIST) 7. Progression free survival at 12 months where progression is determined by mRECIST Previous secondary outcome measures: 1. Radiological response rate (RECIST criterion) measured at baseline, Day 60 and then every 3 months thereafter 2. Rate of change in the tumour marker serum alpha-fetoprotein (AFP) at every visit 3. Assessment of toxicity using National Cancer Institute common terminology criteria for adverse events version 4.02 (NCI-CTCAE version 4) at every visit 4. Immune response rate at every visit 5. Overall survival |
| Overall study start date | 06/01/2014 |
| Overall study end date | 30/11/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 48 |
| Participant inclusion criteria | Current participant inclusion criteria: 1. Histological or cytological diagnosis or meet the American Association for the Study of Liver Diseases (AASLD) criteria for diagnosis of HCC and at least one unidimensional lesion measurable according to the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) by CT-scan or MRI 2. Suitable for transcatheter arterial chemoembolization (TACE) 3. Aged >18 years and estimated life expectancy >6 months 4. Not a candidate for surgical resection or transplantation 5. No previous chemotherapy, radiotherapy, immunotherapy or other experimental treatment for HCC prior to entry into the trial 6. ECOG performance status <= 2 7. Adequate haematological function: Hb >9g/L, Absolute neutrophil count >1.5x109/L, platelet count >50x109/L 8. Bilirubin < 50 umol/L , AST or ALT < 5 x ULN 9. Adequate renal function: Cockroft and Gault estimation > 40ml/min 10. INR less than or equal to 1.5 11. ChildPugh score ≤ 7 12. Women of childbearing potential should have a negative pregnancy test prior to trial entry 13. Women of childbearing potential and men who have partners of childbearing potential must be willing to practise effective contraception for the duration of the study and for six months after the completion of treatment. 14. Written informed consent 15. Suitable veins for access with 17G fistula needle Previous participant inclusion criteria: 1. Histological or cytological diagnosis or meet the American Association for the Study of Liver Diseases (AASLD) criteria for diagnosis of HCC and at least one unidimensional lesion measurable according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria by CT scan or MRI 2. Suitable for transcatheter arterial chemoembolization (TACE) 3. Aged >18 years and estimated life expectancy >6 months 4. Not a candidate for surgical resection or transplantation 5. No previous chemotherapy, radiotherapy, immunotherapy or other experimental treatment for HCC prior to entry into the trial 6. ECOG performance status <= 2 7. Adequate haematological function: Hb >9g/L, Absolute neutrophil count >1.5x109/L, platelet count >50x109/L 8. Bilirubin < 50 umol/L , AST or ALT < 5 x ULN 9. Adequate renal function: Cockroft and Gault estimation > 40ml/min 10. INR less than or equal to 1.5 11. ChildPugh score < 7 12. Women of childbearing potential should have a negative pregnancy test prior to trial entry 13. Women of childbearing potential and men who have partners of childbearing potential must be willing to practise effective contraception for the duration of the study and for three months after the completion of treatment. 14. Written informed consent |
| Participant exclusion criteria | Current participant exclusion criteria as of 12/02/2019: 1. Extrahepatic metastasis 2. Prior embolisation, systemic or radiation therapy for HCC 3. Investigational therapy or major surgery within 4 weeks of trial entry 4. Any ablative therapy [radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI)] for HCC [this should not exclude patients if target lesion(s) have not been treated and occurred >6 weeks prior trial entry] 5. Child Pugh score >7 6. Hepatic encephalopathy 7. Ascites refractory to diuretic therapy 8. Documented invasion of the main portal vein 9. Hypersensitivity to intravenous contrast agents 10. Active clinically serious infection >grade 2 NCI-CTC version 4.0 within preceding two weeks 11. Pregnant or lactating women 12. History of second malignancy except those treated with curative intent more than three years previously without relapse and nonmelanotic skin cancer or cervical carcinoma in situ 13. Evidence of severe or uncontrolled systemic diseases, congestive cardiac failure >NYHA class 2, myocardial infarction (MI) within 6 months or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial 14. Psychiatric or other disorder likely to impact on informed consent 15. Known history of HIV 16. Patient is unable and/or unwilling to comply with treatment and trial instructions 17. Patients with active autoimmune disorder 18. Hypersensitivity to cyclophosphamide or to any of its metabolites 19. Current cystitis infection 20. Urinary outflow obstruction Previous participant exclusion criteria: 1. Extrahepatic metastasis 2. Prior embolisation, systemic or radiation therapy for HCC 3. Investigational therapy or major surgery within 4 weeks of trial entry 4. Any ablative therapy [radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI)] for HCC [this should not exclude patients if target lesion(s) have not been treated and occurred >6 weeks prior trial entry] 5. Child Pugh score >7 6. Hepatic encephalopathy 7. Ascites refractory to diuretic therapy 8. Documented invasion of the main portal vein 9. Hypersensitivity to intravenous contrast agents 10. Active clinically serious infection >grade 2 NCI-CTC version 4.0 (appendix 7) within preceding two weeks 11. Pregnant or lactating women 12. History of second malignancy except those treated with curative intent more than three years previously without relapse and nonmelanotic skin cancer or cervical carcinoma in situ 13. Evidence of severe or uncontrolled systemic diseases, congestive cardiac failure >NYHA class 2, myocardial infarction (MI) within 6 months or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial 14. Psychiatric or other disorder likely to impact on informed consent 15. Known history of HIV 16. Patient is unable and/or unwilling to comply with treatment and trial instructions 17. Patients with active autoimmune disorder |
| Recruitment start date | 06/01/2014 |
| Recruitment end date | 30/09/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom
NG7 2UH
United Kingdom
Aintree University Hospital
Liverpool
L9 7A
United Kingdom
L9 7A
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
National Institute for Health Research (NIHR) (UK) - EME grant
No information available
Results and Publications
| Intention to publish date | 30/11/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is intended that the results of this trial will be submitted for publication in a peer reviewed journal 12 months after the trial end date. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
06/09/2019: The following changes were made:
1. The recruitment end date was changed from 30/08/2019 to 30/09/2019.
2. The overall trial end date was changed from 30/09/2019 to 30/11/2020.
3. The intention to publish date was changed from 30/09/2020 to 30/11/2021.
12/02/2019: The following changes were made:
1. The public title was changed from Immunotace to ImmunoTACE.
2. The protocol/serial number was changed from VERSION 2 : RG_10-148 to VERSION 9 : RG_10-148.
3. The study hypothesis was updated.
4. The primary outcome measure was updated.
5. The secondary outcome measures were updated.
6. The participant inclusion criteria was updated.
7. The participant exclusion criteria was updated.
8. The recruitment end date was updated from 30/08/2018 to 30/08/2019.
9. The trial participating centres were updated.
10. The target number of participant was changed from 70 to 48.
07/02/2018: The following changes were made:
1. Recruitment end date was changed from 06/01/2017 to 30/08/2018.
2. Overall trial end date was changed from 06/01/2017 to 30/09/2019.
3. Publication & dissemination plan and participant level data were added.
09/03/2016: Link to Cancer Help UK lay summary added.
