Condition category
Cancer
Date applied
28/10/2013
Date assigned
11/12/2013
Last edited
12/02/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Prof David Adams

ORCID ID

Contact details

I-ACT Team
CRCTU
5th Floor East
Institute of Translational Medicine
Heritage Building
Mindelsohn Way
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2011-001690-62

ClinicalTrials.gov number

Protocol/serial number

VERSION 9 : RG_10-148

Study information

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)

Acronym

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

UK National Ethics committee - NRES Committee West Midlands - Coventry and Warwickshire; Ref: 11/WM/0367

Study design

Phase II randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Hepacellular Carcinoma

Intervention

Dendritic cell vaccine, Cyclophosphamide, TACE (standard treatment)

Intervention type

Drug

Phase

Phase II

Drug names

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 trial start date

06/01/2014

Overall trial end date

30/09/2019

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

48

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

30/08/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Aintree University Hospital
Liverpool
L9 7A
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research (NIHR) (UK) - EME grant

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/09/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.