Decitabine/carboplatin combination treatment protocol for metastatic melanoma
- Conditions
- Metastatic melanomaCancer - Malignant melanoma
- Registration Number
- ACTRN12616000440426
- Lead Sponsor
- niversity of Newcastle
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 10
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
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.[Week 9 post commencement of treatment];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.[9 weeks post commencement of treatment]
- Secondary Outcome Measures
Name Time Method 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.[9 weeks post commencement of treatment]