Ignite Creation Date:
2025-12-24 @ 9:58 PM
Ignite Modification Date:
2026-01-01 @ 1:07 PM
Study NCT ID:
NCT00925132
Status:
TERMINATED
Last Update Posted:
2017-07-02
First Post:
2009-06-18
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Treatment of Resistant Metastatic Melanoma Using Decitabine, Temozolomide and Panobinostat
Sponsor:
University of Iowa
Organization:
Study Overview
Official Title:
Phase Ib/II: Epigenetic Modification of Chemosensitivity and Apoptosis in Metastatic Melanoma: Treatment of a Resistant Disease Using Decitabine, Temozolomide and Panobinostat
Status:
TERMINATED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Change in the number of approved drugs for metastatic melanoma
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to treat metastatic melanoma with a combination of standard chemotherapy (decitabine and Temozolomide in a dose escalation scheme) with an study drug called panobinostat. This combination is proposed to unlock genes that may contribute to mechanisms that cause tumor growth.
The primary objectives of this study are:
* To evaluate the safety and tolerability of the proposed schedule of decitabine, temozolomide and panobinostat in the treatment of metastatic melanoma.
* To define any Dose Limiting Toxicity (DLT) and maximum tolerated dose (MTD) of the combination of decitabine, temozolomide and panobinostat.
The primary objectives of this study are:
* To evaluate the safety and tolerability of the proposed schedule of decitabine, temozolomide and panobinostat in the treatment of metastatic melanoma.
* To define any Dose Limiting Toxicity (DLT) and maximum tolerated dose (MTD) of the combination of decitabine, temozolomide and panobinostat.
Detailed Description:
Most chemotherapeutics target rapidly proliferating cells, leaving quiescent cells and those with extended cell cycles unaffected. The investigators propose that this combination of decitabine, temozolomide, and panobinostat will target both melanoma stem cells and rapidly proliferating melanoma cells. The use of two drugs that regulate gene expression epigenetically (panobinostat and decitabine) in combination with a chemotherapeutic agent (temozolomide) is hypothesized to:
* induce expression genes (e.g., Apaf-1) that increase chemosensitivity of tumor cells and enhance apoptosis
* potentiate the cytotoxic effect of temozolomide by epigenetic modulation, and
* induce proliferation and differentiation of tumor stem cells, thus enabling senescence and apoptosis.
Secondary objectives:
* To measure overall survival
* To measure the time to progression of patients treated with this combination in comparison to patients treated historically with DTIC (the current standard of care).
* To evaluate treatment response with FDG PET and compare FDG PET with conventional imaging for treatment response assessment.
* induce expression genes (e.g., Apaf-1) that increase chemosensitivity of tumor cells and enhance apoptosis
* potentiate the cytotoxic effect of temozolomide by epigenetic modulation, and
* induce proliferation and differentiation of tumor stem cells, thus enabling senescence and apoptosis.
Secondary objectives:
* To measure overall survival
* To measure the time to progression of patients treated with this combination in comparison to patients treated historically with DTIC (the current standard of care).
* To evaluate treatment response with FDG PET and compare FDG PET with conventional imaging for treatment response assessment.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: