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Trial registered on ANZCTR


Registration number
ACTRN12611001136998
Ethics application status
Approved
Date submitted
28/10/2011
Date registered
31/10/2011
Date last updated
17/01/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination therapy with chemotherapy and immune therapy for metastatic melanoma. Protocol: GPH 11/14.
Scientific title
Evaluation of chemotherapy followed by multivalent dendritic cell vaccines and Ipilimumab for Stage IV metastatic melanoma.
Secondary ID [1] 273274 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic melanoma 279038 0
Condition category
Condition code
Cancer 279225 279225 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive 3 intravenous infusions of Fotemustine 100mg/m2/week for three weeks followed by 3 intradermal vaccinations with 3-6x106 mature, autologous DC treated with tumour lysate (2ug of protein per ml) and immune adjuvants (Zometa, OK432, and KRN7000) at 2 weekly intervals. The participant will then receive four intravenous infusions of Ipilimumab at 3mg/kg per dose at three weekly intervals, concurrently with further DC vaccination. After completion of Ipilimumab, patients will then receive at least four further DC vaccinations at fortnightly intervals until study completion or disease progression.
Intervention code [1] 269617 0
Treatment: Other
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 279855 0
Overall Response (OR) and Time To Progression (TTP) rates will be measured via CT-PET scan in accordance with RESIST Criteria Guidelines. A CT scan of Head (at baseline but only repeated if initially positive or clinically indicated), Chest, Abdomen and Pelvis will be performed Pre-Treatment, D44 and D163. Participants will undergo monthly clinical review for disease progression and autoimmune side effects after D163. Restaging CT and MRI scans will be done every three months or with the development of new symptoms suggestive of disease progression, whichever is earlier.
Timepoint [1] 279855 0
3 year follow-up following End of Treatment
Primary outcome [2] 279856 0
Response rates with the present sequential therapy compared to historical, published studies with Ipilimumab alone or Ipilimumab+ peptide vaccines
Timepoint [2] 279856 0
3 year follow-up following End of Treatment
Secondary outcome [1] 294589 0
Laboratory correlates immune response to melanoma
Timepoint [1] 294589 0
3 year follow-up following End of Treatment

Eligibility
Key inclusion criteria
1) Patients with metastatic stage IV metastatic melanoma and measurable disease as defined by the most recently published RECIST criteria.
2) Written informed consent
3) ECOG performance status 0, 1 or 2
4) Subject judged to be able to safely undergo leukapheresis
5) Age greater than or equal to 16 years.
6) Life expectancy estimated to be greater than 4 months
7) Availability of tumour sample or an alternative source of tumour antigen
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Any concurrent therapy with possible activity against the patient’s malignancy (local radiotherapy on lesions not essential for study evaluation is allowed)
2) Concurrent therapy with any agent known to have immune modulating activity
3) Any therapy with possible activity against the patient’s malignancy in the month preceding administration of first dose of study therapy
4) Patient unable to undergo leukapheresis due to serious co-existing medical conditions (particularly cardiac or cardiovascular) or for other reasons
5) ECOG > 2
6) Pregnant or breast feeding or at risk for becoming pregnant within 3 months of enrolment
7) HIV, Hepatitis B or Hepatitis C positive
8) Patients with history of autoimmune disease affecting the liver, gastrointestinal tract (e.g. ulcerative colitis or Crohn's disease), neurological system (including Guillaine Barre Syndrome and Myasthenia Gravis) and autoimmune pituitary or adrenal disease.
9) Active CNS disease requiring steroids

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)
Participants who meet the eligibility criteria will be enrolled in a sequential, nonrandomized procedure.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The accrual of subjects is not randomized.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Open label Phase I study to determine the overall response rates to sequential therapy with chemotherapy followed by vaccine therapy and Ipilimumab in patients with previously untreated stage IV metastatic melanoma.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 284106 0
Charities/Societies/Foundations
Name [1] 284106 0
Gallipoli Medical Research Foundation
Address [1] 284106 0
Greenslopes Private Hospital
Newdegate Street
GREENSLOPES QLD 4120
Country [1] 284106 0
Australia
Primary sponsor type
Individual
Name
Andrew Nicol
Address
Suite 14, Greenslopes Specialist Centre, Newdegate Street,
GREENSLOPES QLD 4120
Country
Australia
Secondary sponsor category [1] 269068 0
Charities/Societies/Foundations
Name [1] 269068 0
Gallipoli Medical Research Foundation
Address [1] 269068 0
Greenslopes Private Hospital
Newdegate Street
GREENSLOPES QLD 4120
Country [1] 269068 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 272056 0
Greenslopes Research and Ethics Committee
Ethics committee address [1] 272056 0
Ethics Secretary
Greenslopes Private Hospital
Newdegate street
GREENSLOPES, QLD 4120
Ethics committee country [1] 272056 0
Australia
Date submitted for ethics approval [1] 272056 0
08/03/2011
Approval date [1] 272056 0
09/08/2011
Ethics approval number [1] 272056 0
11/14
Ethics committee name [2] 272058 0
University of Queensland Medical Research Ethics Committee
Ethics committee address [2] 272058 0
Human Ethics
Research and Innovation Division
Cumbrae-Stewart Building (#72)
Research Road
BRISBANE, QLD 4072
Ethics committee country [2] 272058 0
Australia
Date submitted for ethics approval [2] 272058 0
21/06/2011
Approval date [2] 272058 0
14/09/2011
Ethics approval number [2] 272058 0
2011000695

Summary
Brief summary
This study involves treatment with a standard chemotherapy for melanoma in combination with immune therapy.

Fotemustine is a chemotherapy drug that is approved for use in metastatic melanoma. It has been shown to produce responses in 15 % of patients. Other benefits include delaying the onset of metastases to the brain, with its major side effects including nausea and vomiting (generally well controlled with current anti-nausea treatments) and low blood counts that could lead to a risk of bleeding and/or infections.

The main aim of the study is to determine the number of patients who respond to successive treatment with chemotherapy followed by vaccine therapy and Ipilimumab in patients with previously untreated stage IV metastatic melanoma. It is planned to include 50 patients with stage IV metastatic melanoma in this study over a 3 year period.

Who is it for? You may be eligible for this study if you have metastatic stage IV metastatic melanoma, provide written informed consent , an ECOG performance status of 0, 1 or 2, are deemed by your physician to be able to safely undergo leukapheresis, are aged greater than or equal to 16 years, have a life expectancy estimated to be greater than 4 months, and are able to provide a tumour sample or an alternative source of tumour antigen – as arranged by your treating hospital or facility.

Trial Details: There are two components to the immune therapy that the patients will receive. One is treatment with a vaccine comprised of the patients’ own Dendritic Cells (immune system boosters, also known as DC’s), treated in the laboratory with their own tumour (autologous melanoma), plus a number of agents known to help stimulate the immune system. Previous studies have shown response rates (meaning melanoma shrinkage) in 10-25 % of cases at best. The overall survival benefits have not been assessed in large numbers of patients. However in a small trial of 11 patients receiving vaccines similar to (but not identical to) the vaccine being used in this study, 3 remain alive 5 years after study enrolment. The second component of the immune therapy is an antibody (Ipilimumab) that unblocks the protective mechanisms that normally operate to prevent the immune system recognising and damaging one’s own body. With this protective mechanism in place, it is very difficult for vaccines to boost the immune system to recognise and kill the melanoma. Ipilimumab has been shown to prolong survival in patients with metastatic melanoma who have previously failed chemotherapy. Of patients previously treated with chemotherapy and then treated with Ipilimumab, 44% were still alive one year after starting Ipilimumab treatment. In comparison of the patients who did not receive Ipilimumab only 25% were still alive after one year. By combining a vaccine with Ipilimumab, it is expected that the boosted immune system (resulting from the vaccines) will not be prevented from recognising and killing the melanoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33313 0
Address 33313 0
Country 33313 0
Phone 33313 0
Fax 33313 0
Email 33313 0
Contact person for public queries
Name 16560 0
Mr. Ben Evans
Address 16560 0
Gallipoli Medical Research Foundation
Greenslopes Private Hospital
Newdegate Street
GREENSLOPES QLD 4120
Country 16560 0
Australia
Phone 16560 0
+61 7 3394 7284
Fax 16560 0
+61 7 3394 7767
Email 16560 0
EvansBen@ramsayhealth.com.au
Contact person for scientific queries
Name 7488 0
Dr. Andrew Nicol
Address 7488 0
Suite 14, Greenslopes Specialist Centre
Newdegate Street,
GREENSLOPES QLD 4120
Country 7488 0
Australia
Phone 7488 0
+61 7 3324 1233
Fax 7488 0
Email 7488 0
anic9909@bigpond.net.au

No data has been provided for results reporting
Summary results
Not applicable