Ignite Creation Date:
2025-12-24 @ 3:57 PM
Ignite Modification Date:
2026-01-01 @ 5:57 PM
Study NCT ID:
NCT01316692
Status:
TERMINATED
Last Update Posted:
2016-05-30
First Post:
2011-03-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Aurora A Kinase Inhibitor MLN8237 in Treating Patients With Unresectable Stage III-IV Melanoma
Sponsor:
Vanderbilt-Ingram Cancer Center
Organization:
Study Overview
Official Title:
A Phase II Correlative Clinical Trial of MLN8237, a Selective Aurora Kinase A (AURKA) Inhibitor, in Patients With Unresectable Stage III or Stage IV Melanoma Disease
Status:
TERMINATED
Status Verified Date:
2016-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
low accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE: Aurora A kinase inhibitor MLN8237 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well Aurora A kinase inhibitor MLN8237 works in treating patients with unresectable stage III-IV melanoma
Funding Source - FDA OOPD
PURPOSE: This phase II trial is studying how well Aurora A kinase inhibitor MLN8237 works in treating patients with unresectable stage III-IV melanoma
Funding Source - FDA OOPD
Detailed Description:
PRIMARY OBJECTIVES:
I. Estimate the degree of clinical benefit based primarily on objective clinical responses with AURKA inhibitor, MLN8237 in patients with metastatic melanoma in a phase II, 2-stage trial for patients with measurable unresectable disease.
SECONDARY OBJECTIVES:
I. Assess the progression-free survival and overall survival for all patients enrolled.
II. Define toxicities due to MLN8237 and characterize their severity both over a short and prolonged duration of administration.
III. In patients entered on stage 1 of clinical trial whenever possible through pre-treatment biopsy and post-treatment surgical specimen, we will define target inhibition at tumor sites based on: AURKA autophosphorylation (AURKAThr288/AURKA), intra-tumoral drug levels, expression of p53-induced NOXA and PUMA expression, TPX2, (by IHC) and TUNEL as markers of apoptosis, cell cycle changes (mitotic index), proliferation (Ki-67), aneuploidy, and AKT phosphorylation.
IV. All phase II trial patients enrolled on the 2nd stage will have pre- and post-treatment biopsies (post-day 7+/-3 days) to demonstrate that AURKA is inhibited based on autophosphorylation AURKA/AURKA\^Thr 288, Histone H3 (at S10) phosphorylation, AKT phosphorylation, cell cycle changes (mitotic index), TPX2 (by IHC), proliferation (Ki-67), aneuploidy, and p53-induced NOXA and PUMA expression, and TUNEL as markers of apoptosis.
V. Demonstrate any correlation between MLN8237 induced target inhibition at tumor sites and clinical benefit of MLN8237.
VI. Characterize the de novo molecular mutational profile of the melanomas from all patients entered using a developed SNaPshot assay for melanoma in addition loss of regulatory proteins (i.e., PTEN), DNA copy numbers and gene expression (AURKA), and autophosphorylation of AURKA as well as AURKA localization by IHC.
OUTLINE: Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 5 years.
I. Estimate the degree of clinical benefit based primarily on objective clinical responses with AURKA inhibitor, MLN8237 in patients with metastatic melanoma in a phase II, 2-stage trial for patients with measurable unresectable disease.
SECONDARY OBJECTIVES:
I. Assess the progression-free survival and overall survival for all patients enrolled.
II. Define toxicities due to MLN8237 and characterize their severity both over a short and prolonged duration of administration.
III. In patients entered on stage 1 of clinical trial whenever possible through pre-treatment biopsy and post-treatment surgical specimen, we will define target inhibition at tumor sites based on: AURKA autophosphorylation (AURKAThr288/AURKA), intra-tumoral drug levels, expression of p53-induced NOXA and PUMA expression, TPX2, (by IHC) and TUNEL as markers of apoptosis, cell cycle changes (mitotic index), proliferation (Ki-67), aneuploidy, and AKT phosphorylation.
IV. All phase II trial patients enrolled on the 2nd stage will have pre- and post-treatment biopsies (post-day 7+/-3 days) to demonstrate that AURKA is inhibited based on autophosphorylation AURKA/AURKA\^Thr 288, Histone H3 (at S10) phosphorylation, AKT phosphorylation, cell cycle changes (mitotic index), TPX2 (by IHC), proliferation (Ki-67), aneuploidy, and p53-induced NOXA and PUMA expression, and TUNEL as markers of apoptosis.
V. Demonstrate any correlation between MLN8237 induced target inhibition at tumor sites and clinical benefit of MLN8237.
VI. Characterize the de novo molecular mutational profile of the melanomas from all patients entered using a developed SNaPshot assay for melanoma in addition loss of regulatory proteins (i.e., PTEN), DNA copy numbers and gene expression (AURKA), and autophosphorylation of AURKA as well as AURKA localization by IHC.
OUTLINE: Patients receive oral Aurora A kinase inhibitor MLN8237 every 12 hours on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 5 years.
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2010-02322 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| R01FD003522 | FDA | None | https://reporter.nih.gov/quic… | View |