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Trial registered on ANZCTR


Trial ID
ACTRN12613000866707
Ethics application status
Approved
Date submitted
22/07/2013
Date registered
6/08/2013
Date last updated
28/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial of adoptive T-cell immunotherapy for patients with Epstein-Barr virus-associated nasopharyngeal carcinoma.
Scientific title
Phase I/II open-label clinical trial of autologous Epstein-Barr virus-specific T cell therapy as consolidative treatment following chemotherapy for metastatic EBV-associated nasopharyngeal carcinoma.
Secondary ID [1] 282876 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic nasopharyngeal carcinoma 289695 0
Condition category
Condition code
Cancer 290014 290014 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EBV-specific T cell adoptive immunotherapy. Initially, all patients will receive standard chemotherapy (first-line intravenous gemcitabine 1000mg/m2 in combination with cisplatin/carboplatin for up to 6 cycles, according to standard clinical practices). Following its completion, the immunotherapy will commence at the clinician’s discretion. A dose of 2x10^7/m^2 LMP/EBNA1-specific autologous T cells will be given by intravenous infusion at weeks 2,4,6,8,10 and 12
Intervention code [1] 287578 0
Treatment: Other
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290060 0
Primary endpoint will be progression free survival. Progression free survival is defined as the time from recruitment to time of disease progression, death or last follow-up, whichever occurs first. It is anticipated that treatment of 30 NPC patients (including 5 percent dropout) with metastatic disease will allow us to have preliminary assessment of the efficacy of such combined chemotherapy and immunotherapy approach. Assessed by: MRI/CT, Nasendoscopy
Timepoint [1] 290060 0
Time point: MRI/CT scans will be done as per standard clinical practice, usually prior to receiving any chemotherapy, after receiving 3 cycles, and then at 6-12 monthly intervals. Where clinically indicated nasendoscopy will be performed. Blood tests will be done at baseline 1, 2, 4, 6, 8, 10, 12, 16, 24 and 38 weeks. Follow-up is for 6 months following the final infusion.
Primary outcome [2] 290061 0
Another primary endpoint will be assessment of tolerability and safety of administering a combination therapy based on chemotherapy and autologous LMP/EBNA1-specific T cells Assessed by: Physical examinations, vital signs, bloods test for FBC, E/LFT as well as for immunological and virological parameters
Timepoint [2] 290061 0
Time point: Baseline, 1, 2, 4, 6, 8, 10, 12, 16, 24 and 38 weeks.
Secondary outcome [1] 303855 0
Our secondary endpoint will be overall survival.
Timepoint [1] 303855 0
Overall survival will be assessed as the time from enrollment until death from progressive NPC disease. The maximum duration of follow-up is 3 years post-treatment.
Secondary outcome [2] 303933 0
Immune functional and correlative studies (induction and persistence of EBV-specific immune response and changes in EBV DNA levels).
Timepoint [2] 303933 0
Immune functional and correlative studies will be done by collecting blood and isolating white blood cells for immunological analysis and EBV DNA load analysis at baseline 1, 2, 4, 6, 8, 10, 12, 16, 24 and 38 weeks.

Eligibility
Key inclusion criteria
1. Age 18 years or above
2. Histologically proven NPC
3. Provision of Informed consent (approved hospital interpreters will be used for patients who do not have sufficient understanding of English for informed consent to be obtained without the use of an interpreter)
4. ECOG performance status 0, 1, or 2
5. Life expectancy of at least 6 months, as determined by the clinical investigator
6. Adequate haematological and biochemical function
7. No history of other malignancy other than basal cell carcinoma of skin
8. Completion of a medical questionnaire
9. Patient is suitable to commence standard chemotherapy for metastatic NPC
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. EBV negative tumour
2. Positive serology and/or NAT for HIV
3. Positive serology and/or nucleic acid testing (NAT) for human immunodeficiency virus
4. Serology and/or NAT indicating active HBV infection or carrier status for HBV (N.B. Positive serology for HBV indicating previous but cleared infection with HBV would not be an exclusion criteria)
5. Serology and/or NAT indicating active HCV infection
6. Positive serology for syphilis or HTLV I/II
7. Significant non-malignant disease (e.g. severe cardiac or respiratory dysfunction)
8. Psychiatric, addictive or any conditions which may compromise the ability to participate in this trial
9. Inability to provide informed consent, including patients with severe cognitive impairment, intellectual disability or mental illness
10. Prior cancers, except those diagnosed greater than 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than 5 percent, or successfully treated nonmelanoma skin cancer, or carcinoma in situ of the cervix.
11. Currently receiving immunosuppressive therapy, including corticosteroids. At the discretion of the clinical investigator the patient can receive anti-emetics
12. Pregnant, or unwilling to use adequate contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Nil
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Overall survival and progression free survival will be estimated using Kaplan-Meier method separately. Median progression free survival will be determined using this methodology and 95% confidence interval will be calculated. Response rate and clinical benefit rate will be estimated with 95% confidence interval. Survival curves will be estimated by the Kaplan-Meier method and differences will be tested using log-rank test statistics. p values less than 0.05 will be considered statistically significant. Historically, NPC patients with recurrent/metastatic disease receiving conventional chemotherapy at Queen Mary Hospital (Hong Kong) have median progression free survival of 6 months and overall survival of 10.3 months. If we are to compare to the historical median progression free survival time of 6 months, then a median survival time of 10.6 months in our study of 30 patients will allow us to conclude with 5% significance and 80% power that the therapy has increased median progression free survival time. This calculation is performed assuming an accrual time of 36 months and follow-up of 6 months.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 1352 0
Princess Alexandra Hospital - Woolloongabba
Recruitment outside Australia
Country [1] 5237 0
Hong Kong
State/province [1] 5237 0

Funding & Sponsors
Funding source category [1] 287661 0
Charities/Societies/Foundations
Name [1] 287661 0
QIMR Berghofer Medical Research Institute Immunotherapy Flagship Program
Address [1] 287661 0
300 Herston Road, Herston, Brisbane, QLD, 4006
Country [1] 287661 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road, Herston, Brisbane, QLD, 4006
Country
Australia
Secondary sponsor category [1] 286399 0
None
Name [1] 286399 0
Address [1] 286399 0
Country [1] 286399 0
Other collaborator category [1] 277532 0
Hospital
Name [1] 277532 0
Princess Alexandra Hospital (PAH)
Address [1] 277532 0
199 Ipswich Road, Woolloongabba,
Queensland, Australia 4102
Country [1] 277532 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289624 0
Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 289624 0
The Queensland Institute of Medical Research HREC
Queensland Institute of Medical Research
300 Herston Rd
Herston QLD 4006

Ethics committee country [1] 289624 0
Australia
Date submitted for ethics approval [1] 289624 0
Approval date [1] 289624 0
14/06/2013
Ethics approval number [1] 289624 0
P1486
Ethics committee name [2] 293580 0
Metro South Human Research Ethics Committee
Ethics committee address [2] 293580 0
199 Ipswich Road
Woolloongabba, QLD 4102
Ethics committee country [2] 293580 0
Australia
Date submitted for ethics approval [2] 293580 0
Approval date [2] 293580 0
19/05/2014
Ethics approval number [2] 293580 0
HREC/13/QPAH/436

Summary
Brief summary
This study is evaluating the effect of using T cell immunotherapy following standard chemotherapy for the treatment of nasopharyngeal cancer (NPC).

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with metastatic nasopharyngeal cancer and your clinician is planning to treat you with standard chemotherapy.

Trial details
All participants in this study will receive standard chemotherapy with gemcitabine and cisplatin according to their clinician’s standard clinical care. Following this, they will undergo the experimental immunotherapy. This involves infusing Epstein-Barr Virus (EBV) specific T-cells intravenously (i.e. directly into the vein) up to 6 times, at fortnightly intervals.

Participants will be regularly assessed for up to 38 weeks in order to evaluate their response to treatment, and the safety and tolerability of treatment.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 41622 0
Prof Rajiv Khanna
Address 41622 0
QIMR Berghofer Centre for Immunotherapy and Vaccine Development
Tumour Immunology Laboratory
Level 10, CBCRC, 300 Herston Road
Herston, QLD 4006
Country 41622 0
Australia
Phone 41622 0
+61 7 3362 0385
Fax 41622 0
+61 7 3845 3510
Email 41622 0
Rajiv.Khanna@qimrberghofer.edu.au
Contact person for public queries
Name 41623 0
Dr Michelle Neller or Katherine Matthews
Address 41623 0
QIMR Berghofer Medical Research Institute
300 Herston Road
Herston, QLD 4006
Country 41623 0
Australia
Phone 41623 0
+61-7-3362 0412
Fax 41623 0
+61 7 3845 3510
Email 41623 0
immunotherapy@qimrberghofer.edu.au
Contact person for scientific queries
Name 41624 0
Prof Rajiv Khanna
Address 41624 0
QIMR Berghofer Medical Research Institute
QIMR Berghofer Centre for Immunotherapy and Vaccine Development
Tumour Immunology Laboratory
300 Herston Road
Herston, QLD 4006
Country 41624 0
Australia
Phone 41624 0
+61 7 3362 0385
Fax 41624 0
+61 7 3845 3510
Email 41624 0
Rajiv.Khanna@qimrberghofer.edu.au