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Trial registered on ANZCTR


Registration number
ACTRN12612001069842
Ethics application status
Approved
Date submitted
11/09/2012
Date registered
5/10/2012
Date last updated
23/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
EMOTIV Trial - Enhancing Melanoma Outcomes using a Timed Immunotherapy Vaccine
Scientific title
The effect of timed co-ordinated vaccine and chemotherapy delivery on complete response rate and overall survival in patients with advanced melanoma
Secondary ID [1] 281098 0
Nil
Universal Trial Number (UTN)
U1111-1133-8625
Trial acronym
EMOTIV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Stage IIIb/c and IV Melanoma 287256 0
Condition category
Condition code
Cancer 287582 287582 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - Control Arm: 0.3 ml VMCL Vaccine Untimed, administered via intra-dermal injection. If progression occurs, then addition of oral chemotherapy (cyclophosphamide -100mg tablet) every 3 weeks, until disease regression/progression. Arm 1 therapies are administered on a regular, pre-determined basis per protocol schedule.
Arm 2 - Test Arm: 0.3 ml VMCL vaccine Timed, administered via intra-dermal injection. If progression occurs, then addition of timed oral chemotherapy (cyclophosphamide - 100mg tablet) as dictated by patients immune system cycle profile (approximately 3 weekly), until disease regression/progression. Arm 2 therapies are co-ordinated with the patient's own immune cycle, as determined by regular blood tests.
Intervention code [1] 285551 0
Treatment: Drugs
Comparator / control treatment
See Arm 1 - Control Arm above.
Control group
Active

Outcomes
Primary outcome [1] 287839 0
Complete response rate as defined by WHO criteria, utilising laboratory markers and CT scans
Timepoint [1] 287839 0
Assessments at 3, 6, 9 and 12 months for each patient and collectively 1, 2 and 5 years.
Primary outcome [2] 288042 0
Overall survival
Timepoint [2] 288042 0
Assessments at 3, 6, 9 and 12 months for each patient and collectively 1, 2 and 5 years.
Secondary outcome [1] 298913 0
Toxicity as assessed by any reported SAE's.
Timepoint [1] 298913 0
Ongoing assessment for up to 18mo from enrollment and recorded at time of treatment or SAE.
Secondary outcome [2] 299327 0
Overall response rate as assessed by CT scans
Timepoint [2] 299327 0
Assessments at 3, 6, 9 and 12 months for each patient and collectively 1, 2 and 5 years.
Secondary outcome [3] 299328 0
Disease progression as assessed by CT scans
Timepoint [3] 299328 0
Assessments at 3, 6, 9 and 12 months for each patient and collectively 1, 2 and 5 years.
Secondary outcome [4] 299329 0
Immunologic parameters as assessed by laboratory markers
Timepoint [4] 299329 0
Assessments at 3, 6, 9 and 12 months for each patient and collectively 1, 2 and 5 years.

Eligibility
Key inclusion criteria
18 - 80 years of age. ECOG 0-2. Evaluable metastases. Primary cutaneous melanoma. Advanced surgically non-resectable AJCC Stage IIIB/IIIC or IV. Able to give informed consent. Tumour volume < 20cm diameter or <70% of organ replacement.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of another primary invasive cancer (not BCC, SCC or resected in-situ malignancy)
Untreated brain mets
Extremely extensive disease
Bone mets only
High dose oral steroid therapy
Pregnancy or lactation
Severe atopia
Severe cachexia
Immunodeficiency
HIV
Hep B or C +ve

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation and allocation procedure being carried out by external party. (NHMRC)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Method is permuted block randomisation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
All participants receive the same initial intervention but at differing times. If disease progression occurs, each arm then proceeds to the same second intervention, also occurring at different times.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size was selected to ensure the standard error of the observed response rate was = 0.1 and to permit a satisfactory estimate of response rate. The pilot study design is in accordance with previous literature determining sample size for prediction of larger study testing (Hertzog 2008). The anticipated predicted difference is for an approximate doubling of the CR rate in the test (timed therapy) group, over the control (untimed therapy) group. An early stopping rule according to the method of Gehan (1961) was incorporated with the response rate of interest set at 15%. Descriptive statistics will be generated for response efficacy, toxicity and survival end-points. The median time to progression (TTP) will be estimated using Kaplan–Meier survival curves (STATA-1). Data between groups will be analysed by t-test or the Mann–Whitney U-test and Spearman’s method will be used for correlations. The log-rank test will be used to compare survival between patients with progressive and SD. Significance will be assumed if P < 0.05.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1936 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 5608 0
5000
Recruitment postcode(s) [2] 5609 0
5159
Recruitment postcode(s) [3] 5610 0
5010
Recruitment postcode(s) [4] 5611 0
5076
Recruitment postcode(s) [5] 5612 0
5042
Recruitment postcode(s) [6] 5613 0
5062
Recruitment postcode(s) [7] 5614 0
5066
Recruitment postcode(s) [8] 5616 0
5074
Recruitment postcode(s) [9] 5617 0
5038
Recruitment postcode(s) [10] 5619 0
5113
Recruitment postcode(s) [11] 5621 0
5112
Recruitment postcode(s) [12] 5623 0
5118
Recruitment postcode(s) [13] 5624 0
5035
Recruitment postcode(s) [14] 5625 0
5069
Recruitment postcode(s) [15] 5631 0
5037
Recruitment postcode(s) [16] 5632 0
5168
Recruitment postcode(s) [17] 5633 0
5040
Recruitment postcode(s) [18] 5634 0
5243
Recruitment postcode(s) [19] 5636 0
5043
Recruitment postcode(s) [20] 5637 0
5942
Recruitment postcode(s) [21] 5638 0
5033
Recruitment postcode(s) [22] 5639 0
5008
Recruitment postcode(s) [23] 5640 0
5108
Recruitment postcode(s) [24] 5641 0
5169

Funding & Sponsors
Funding source category [1] 285883 0
Government body
Name [1] 285883 0
South Australian Health and Medical Research Institute
Address [1] 285883 0
Level 9
121 King William St
Adelaide SA 5000
Country [1] 285883 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australian Melanoma Research Foundation
Address
AMRF
PO Box 574
Kent Town DC
SA 5071
Country
Australia
Secondary sponsor category [1] 284708 0
None
Name [1] 284708 0
Address [1] 284708 0
Country [1] 284708 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287912 0
Royal Adelaide Hospital HREC
Ethics committee address [1] 287912 0
Royal Adelaide Hospital
Research Ethics Committee
North Terrace
Adelaide SA 5000
Ethics committee country [1] 287912 0
Australia
Date submitted for ethics approval [1] 287912 0
29/08/2012
Approval date [1] 287912 0
28/06/2013
Ethics approval number [1] 287912 0
120924

Summary
Brief summary
This study is evaluating the effect of timed vaccine and chemotherapy delivery in advanced melanoma patients. You may be eligible to join this study if you are a male or female aged 18 years or above who has been diagnosed with advanced melanoma (Stage IV or IIIB/IIIC) that cannot be treated with surgery. Participants in this trial will be randomly allocated to one of two groups. Participants in groups one and two will both receive the VCML vaccine. Group one will receive regular, pre-determined vaccinations whereas Group two will have their vaccination times determined by blood test results. If disease progression occurs, then participants in group one will receive oral chemotherapy treatment on pre-determined dates, whereas participants in group 2 will receive oral chemotherapy at times determined by the results of blood tests. The treatment in group 1 will not be timed in this way. All participants will be assessed on a regular basis for a period of up to 5 years in order to determine whether treatment response and overall survival differ between groups. This will enable us to determine whether the timing of vaccine or chemotherapy administration can improve treatment response.
Trial website
Trial related presentations / publications
Coventry BJ etal Immuno-Chemotherapy Using Repeated Vaccine Treatment Can Produce Successful Clinical Responses in Advanced Metastatic Melanoma. Journal of Cancer Therapy, 2010, 1: 205-213.
Public notes

Contacts
Principal investigator
Name 34624 0
A/Prof Brendon Coventry
Address 34624 0
Level 8 AHMS Building
North Terrace
Adelaide SA 5000
Country 34624 0
Australia
Phone 34624 0
+61 8 83136037
Fax 34624 0
Email 34624 0
brendon.coventry@adelaide.edu.au
Contact person for public queries
Name 17871 0
A/Prof Brendon J Coventry
Address 17871 0
Level 8 AHMS Building
North Terrace
Adelaide SA 5000
Country 17871 0
Australia
Phone 17871 0
+61 8 83136037
Fax 17871 0
Email 17871 0
brendon.coventry@adelaide.edu.au
Contact person for scientific queries
Name 8799 0
A/Prof Brendon J Coventry
Address 8799 0
Level 8 AHMS Building
North Terrace
Adelaide SA 5000
Country 8799 0
Australia
Phone 8799 0
+61 8 83136037
Fax 8799 0
Email 8799 0
brendon.coventry@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary