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Trial registered on ANZCTR


Registration number
ACTRN12616000440426
Ethics application status
Approved
Date submitted
1/04/2016
Date registered
6/04/2016
Date last updated
24/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Decitabine/carboplatin combination treatment protocol for metastatic melanoma
Scientific title
Pilot Early phase II study of Decitabine and Carboplatin in patients with advanced melanoma
Secondary ID [1] 288906 0
None
Universal Trial Number (UTN)
Trial acronym
PRIME001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic melanoma 298241 0
Condition category
Condition code
Cancer 298382 298382 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
First month- Decitabine 7mg/m2 intravenous infusion (IVI)/day for 5 days (D1-D5) followed by Carboplatin Area under the curve (AUC) 5 as per the Calvert formula, IVI on D8; Week 3 and Week 4- no treatment.

Second month- repeat above starting at Week 5, Day 29.

All doses administered and logged on site by study staff.
Intervention code [1] 294370 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297854 0
Tumour biopsy will be used for the composite outcome of DNA methylation (whole genome bisulfite sequencing and ELISA assay), XPC mRNA and XPC protein levels. Statistically significant differences in methylation and XPC levels will be tested before and after treatment using paired t-test with Bonferroni correction.
Timepoint [1] 297854 0
Week 9 post commencement of treatment
Primary outcome [2] 297855 0
Tumour biopsy will be used for immunohistochemistry to assess the composite outcome of immune-response markers: CD4 and CD8 inside tumour, number of tumour cells with PDL1 expression, CD8 with PDL1 expression, CD8 with CD45RO expression, CD8 with granzyme B, TIM3, perforin as described in Tumeh et al. 2015. Blood collected will be tested for immune activation profile and INF gamma signature. All data will be inccluded for composite outcome and will be tested before and after treatment using paired t-test with Bonferroni correction.
Timepoint [2] 297855 0
9 weeks post commencement of treatment
Secondary outcome [1] 322450 0
Quantify response rate (RR) using RECIST 1.1 criteria at completion of 2 cycles. This data will be used to calculate sample size for larger Phase II study.
Timepoint [1] 322450 0
9 weeks post commencement of treatment

Eligibility
Key inclusion criteria
1. Age>= 18 years
2. Before study enrolment written informed consent to participate in the trial must be given according to ICH/GCP and national/local regulations
3. Resistance to all approved treatments for melanoma
4. Tumour material is mandatory- tumour tissue selected must not be previously irradiated; treatment should start only after complete wound healing from surgery
5. Disease status before first treatment should be documented by full CT scan of brain, chest, abdo and pelvis and PET scan and MRI brain if indicated
6. BRAF mutation status
7. ECOG Performance Status 0,1,2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. mucosal or ocular melanoma
2. CNS metastases
3. Patient demonstrates inadequate organ function- hematologic, hepatic and renal
4. History of pneumonitis, interstitial lung disease, inflammatory bowel disease or active auto-immune disease that required systemic treatment in past 2 years (with use of disease modifying agents, corticosteroids or immune suppressive drugs)
5. History of immune related toxicity to previous immunotherapy of grade 2 or higher except endocrinology related toxicity that is treated and stable and on replacement therapy for adrenal, pituitary or thyroid deficiency (thyroxine, insulin or physiologic corticosteroid therapy allowed)
6. Diagnosis of immunodeficiency
7. Known history of HIV; active Hep B/C
8. Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
9. Patients who received treatment with live vaccines within 30 days prior to first dose of study medication
10. Patient is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used and investigation device within 4 week prior to first dose of treatment
11. History of hematologic or primary solid tumour malignancy, unless no evidence of that disease for 5 years
12. Pregnancy and Contraception- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first dose of study treatment
13. Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last dose of the study drug

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
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistically significant differences in methylation and XPC levels will be tested before and after treatment using paired t-test with Bonferroni correction. Response rate (RR) using RECIST 1.1 criteria will be quantified at completion of 2 cycles. This data will be used to calculate sample size for larger Phase II study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2016
Actual
21/02/2017
Date of last participant enrolment
Anticipated
31/12/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5538 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 13004 0
2298 - Waratah

Funding & Sponsors
Funding source category [1] 293256 0
Charities/Societies/Foundations
Name [1] 293256 0
Ramaciotti Foundation
Country [1] 293256 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Dr
Callaghan, NSW 2308
Country
Australia
Secondary sponsor category [1] 292060 0
None
Name [1] 292060 0
Address [1] 292060 0
Country [1] 292060 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294735 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 294735 0
Research Ethics and Governance Unit
Locked bag 1, New Lambton, NSW, 2305
Ethics committee country [1] 294735 0
Australia
Date submitted for ethics approval [1] 294735 0
18/12/2015
Approval date [1] 294735 0
16/03/2016
Ethics approval number [1] 294735 0
15/12/16/3.08

Summary
Brief summary
The primary purpose of this pilot trial is to examine the efficacy of decitabine in combination with carboplatin for the treatment of metastatic melanoma.
Who is it for?
You may be eligible to participate in this trial if you are aged 18 or over, and have been diagnosed with metastatic melanoma which has been resistant to all previous treatments. Study details
All participants enrolled in this trial will receive combination therapy with two chemotherapy agents, decitabine and carboplatin, according to the following treatment regime. On days 1-5, patients will receive a daily intravenous infusion of decitabine, followed by a single infusion of carboplatin on day 8. There will then be no treatment administered for the remainder of the cycle, until the regime is repeated starting on day 29.
Researchers will perform tests on blood and tumour biopsy samples to examine the efficacy of the treatment in altering tumour cells so that they are more vulnerable to the immune system, and thus treating the cancer. It is hoped that information from this trial will provide preliminary information on the efficacy of decitabine in combination with carboplatin for the treatment of metastatic melanoma, and provide data to inform a larger clinical trial of this therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64874 0
Dr Andre van der Westhuizen
Address 64874 0
Department of Medical Oncology
Calvary Mater hospital
2 Edith Street
Waratah NSW
2298
Country 64874 0
Australia
Phone 64874 0
+61249211561
Fax 64874 0
Email 64874 0
[email protected]
Contact person for public queries
Name 64875 0
Nikola Bowden
Address 64875 0
Hunter Medical Research Institute
c/o - University Dr
Callaghan NSW 2308
Country 64875 0
Australia
Phone 64875 0
+61240420277
Fax 64875 0
Email 64875 0
[email protected]
Contact person for scientific queries
Name 64876 0
Nikola Bowden
Address 64876 0
Hunter Medical Research Institute
c/o - University Dr
Callaghan NSW 2308
Country 64876 0
New Zealand
Phone 64876 0
+61240420277
Fax 64876 0
Email 64876 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23421Study protocolhttps://dx.doi.org/10.1097%2FMD.0000000000020705  
23422Clinical study reportvan der Westhuizen et al. Sequential Decitabine and Carboplatin Induced Stabilisation of Tumour Burden in A Patient with Immunotherapy-Resistant Metastatic Melanoma. Clinical Oncology Case Reports. In Press  

Results publications and other study-related documents

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

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4598Study results articleYes van der Westhuizen et al. Sequential Decitabine an... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIPilot early phase II study of decitabine and carboplatin in patients with advanced melanoma2020https://doi.org/10.1097/md.0000000000020705
N.B. These documents automatically identified may not have been verified by the study sponsor.