Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12609000736246
Ethics application status
Approved
Date submitted
17/08/2009
Date registered
25/08/2009
Date last updated
26/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I trial of dendritic cell vaccination and celecoxib with postoperative radiotherapy and temozolomide for treatment of malignant glioma.
Scientific title
Phase I trial of dendritic cell vaccination and celecoxib with postoperative radiotherapy and temozolomide for treatment of malignant glioma.
Secondary ID [1] 944 0
Queensland Institute of Medical Research project number P984
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant glioma 243450 0
Condition category
Condition code
Cancer 239748 239748 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Autologous dendritic cells pulsed with irradiated autologous tumour cells, formulated in 10% dimethyl sulfoxide, cryopreserved, and thawed just prior to injection. This product will be administered in combination with celecoxib and standard adjuvant radiochemotherapy (ie radiation and temozolomide). Local radiotherapy commences approximately two weeks after surgery. This continues for five days a week, for five weeks. Throughout this period, low dose oral temozolomide is given every day. After this, a higher dose is given for five days every four weeks for six cycles. The first vaccination will be given a week before the completion of the five weeks of radiochemotherapy. Vaccinations will continue every two weeks for six treatments, and then four-six weekly thereafter. Patients will be given the oral non-steroidal anti-inflammatory drug celecoxib (400mg twice daily) over eight weeks continuously, commencing with radio-chemotherapy.
Intervention code [1] 237067 0
Treatment: Other
Comparator / control treatment
None (single group, phase I study)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 240506 0
Safety: safety will be assessed by the incidence of adverse events considered to be associated with the experimental therapy (including haematology and biochemistry).
Timepoint [1] 240506 0
at weeks 6, 8, 10, 12, 14, 16, 22, 26, 30, 34, 28, 42, 52 post surgery
Secondary outcome [1] 257062 0
Tolerability: tolerability of the combined regimen will be assessed via quality of life measures.
Timepoint [1] 257062 0
at weeks 6, 8, 10, 12, 14, 16, 22, 26, 30, 34, 38, 42, 52 post surgery
Secondary outcome [2] 257063 0
General effects on the immune system of standard therapy and experimental intervention assessed by changes in cell counts and immune function in blood samples.
Timepoint [2] 257063 0
at weeks 2, 6, and 16 post surgery
Secondary outcome [3] 257064 0
Efficacy of vaccination on tumour growth will be assessed via magnetic resonance imaging (MRI) scans.
Timepoint [3] 257064 0
at weeks 1, 7, 19, 31 post surgery

Eligibility
Key inclusion criteria
1. Malignant glioma (World Health Organisation grade IV). Preoperative assessment by clinical presentation and Computed tomography (CT) / Magnetic Resonance Imaging (MRI) scans appearance of the lesion will identify suitable candidates. Progression to enrolment will be dependent upon the neuropathological diagnosis being confirmed.
2. Age 18 – 75
3. Macroscopic tumour resection (ie it was felt by the surgeon at operation that all visible tumour was resected; tumour seen on postoperative imaging does not exclude the patient from consideration)
4. Patient undergoing standard postoperative radiotherapy and concurrent temozolomide chemotherapy, followed by post-radiotherapy temozolomide.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of extensive intracranial or intraspinal disease which precludes total macroscopic or subtotal resection.
2. Eastern Cooperative Oncology Group (ECOG) status > 2
3. Documented history of auto-immune disease such as systemic lupus erythematosus (SLE), sarcoidosis, rheumatoid arthritis, glomerulonephritis or vasculitis. Previous use of long term immunosuppressive therapy in recent months. (NB perioperative short term
dexamethasone, which is normal treatment, does not preclude inclusion in the trial)
4. Prior use of any immunotherapeutic agent.
5. Serology indicating active infection with Hepatitis B or C, human immunodeficiency virus (HIV), human T-cell leukemia virus-1 (HTLV-1) or syphilis
6. Significant non-malignant disease (eg severe cardiac or respiratory dysfunction)
7. Pregnancy
8. Presence of another malignancy.
9. Clinically relevant abnormal haematological and biochemical parameters (as assessed by the treating clinician).
10. History of significant cardiac history (ie myocardial infarction < 1year, unstable angina).
11. Severe asthma or previous reactions to any non-steroidal anti-inflammatory medication.
12. If the patient is taking regular medications known to interact with celecoxib (lithium, warfarin, other Non-steroidal anti-inflammatory drugs).
13. Inadequate venous access for leukapheresis.

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
None
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/11/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1999 0
4066

Funding & Sponsors
Funding source category [1] 237443 0
Other
Name [1] 237443 0
Wesley Research Institute
Country [1] 237443 0
Australia
Primary sponsor type
Government body
Name
Queensland Institute of Medical Research
Address
300 Herston Road
Herston
QLD
4006
Country
Australia
Secondary sponsor category [1] 236933 0
None
Name [1] 236933 0
Address [1] 236933 0
Country [1] 236933 0
Other collaborator category [1] 805 0
Commercial sector/Industry
Name [1] 805 0
Briz Brain and Spine
Address [1] 805 0
The Wesley Hospital
Evan Thomson Building
Level 10
Chasely Street
Auchenflower
QLD
4066
Country [1] 805 0
Australia
Other collaborator category [2] 806 0
Hospital
Name [2] 806 0
Wesley Hospital
Address [2] 806 0
451 Coronation Drive, Auchenflower, Brisbane, 4066
Country [2] 806 0
Australia
Other collaborator category [3] 807 0
Hospital
Name [3] 807 0
St Andrew's Hospital
Address [3] 807 0
457 Wickham Tce, Brisbane, 4000
Country [3] 807 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239574 0
Queensland Institute of Medical Research Human Research Ethics Committee (QIMR HREC)
Ethics committee address [1] 239574 0
300 Herston Road, Herston, QLD, 4006
Ethics committee country [1] 239574 0
Australia
Date submitted for ethics approval [1] 239574 0
Approval date [1] 239574 0
26/05/2006
Ethics approval number [1] 239574 0
H0604-013T (P984)

Summary
Brief summary
Gliomas are the most common primary brain tumour in adults and children. For patients with the commonest form, glioblastoma multiforme, the median survival is approximately 1 year. Based on data from our previous trial, we hypothesize that concomitant dendritic cell vaccine therapy and celecoxib, when combined with standard postoperative radiotherapy and temozolomide, is safe and effective in patients with malignant glioma. 10 patients will receive a minimum of six vaccines, and up to 12 where possible (If recurrence or progression does not occur, vaccination will continue for up to 12 vaccinations). Dendritic cell vaccines will be manufactured from the patient’s own blood cells and tumour resected at surgery. Local radiotherapy commences approximately two weeks after surgery. This continues for five days a week, for five weeks. Throughout this period, low dose oral temozolomide is given every day. After this, a higher dose is given for five days every four weeks for six cycles. The first vaccination will be given a week before the completion of the five weeks of radiochemotherapy. Vaccinations will continue every two weeks for six treatments, and then four-six weekly thereafter. Patients will be given the oral non-steroidal anti-inflammatory drug celecoxib (400mg twice daily) over eight weeks continuously, commencing with radio-chemotherapy. Patients will be clinically evaluated at each visit, including an assessment of quality of life. Symptoms and signs of toxicity will be monitored. An MRI scan will also be done at intervals according to standard clinical protocols.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30007 0
Dr Chris Schmidt
Address 30007 0
Queensland Institute of Medical Research
300 Herston Road
Hertson
QLD
4006
Country 30007 0
Australia
Phone 30007 0
+61 7 3362 0313
Fax 30007 0
Email 30007 0
[email protected]
Contact person for public queries
Name 13254 0
Dr David Walker
Address 13254 0
Briz Brain and Spine
The Wesley Hospital
Evan Thomson Building
Level 10
Chasely Street
Auchenflower
QLD
4066
Country 13254 0
Australia
Phone 13254 0
+61 07 3833 2500
Fax 13254 0
+61 07 3833 2511
Email 13254 0
[email protected]
Contact person for scientific queries
Name 4182 0
Dr Chris Schmidt
Address 4182 0
Queensland Institute of Medical Research,
P.O. Box Royal Brisbane Hospital, 4029
Country 4182 0
Australia
Phone 4182 0
+61 07 3362 0313
Fax 4182 0
+ 61 07 3845 3510.
Email 4182 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.