Ignite Creation Date:
2025-12-25 @ 4:52 AM
Ignite Modification Date:
2025-12-26 @ 3:53 AM
Study NCT ID:
NCT02319018
Status:
COMPLETED
Last Update Posted:
2018-10-09
First Post:
2014-12-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Alisertib and Combination Chemotherapy in Treating Patients With Gastrointestinal Tumors
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1 Study of Alisertib (MLN8237) in Combination With mFOLFOX in Gastrointestinal Tumors
Status:
COMPLETED
Status Verified Date:
2018-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of alisertib when given together with combination chemotherapy in treating patients with gastrointestinal tumors. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving alisertib with more than one drug (combination chemotherapy) may be a better treatment for gastrointestinal tumors.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated doses and the recommended phase II doses of modified fluorouracil, leucovorin calcium, oxaliplatin (mFOLFOX) given in combination with alisertib (MLN8237) in patients with gastrointestinal cancers.
SECONDARY OBJECTIVES:
I. To describe any anti-tumor activity associated with this treatment. II. To assess baseline tumor expression by immunohistochemistry of aurora kinase A (AURKA), v-akt murine thymoma viral oncogene homolog 1 (AKT), phosphorylated (phospho)-AKT (serine \[Ser\]473), tumor protein p53 (p53), tumor protein p73 (p73), beta (b)-catenin, v-myc myelocytomatosis viral oncogene homolog (avian) (c-MYC), and cleaved caspase 3.
III. To assess baseline messenger ribonucleic acid (mRNA) expression of AURKA, vascular endothelial growth factor (VEGF), c-MYC, human double minute 2 (HDM2), and cyclin D1 (CCND1), and correlate with response to therapy.
IV. To obtain post-treatment biopsy specimens and confirm target inhibition by assaying for AURKA, phosphorylated (p)AURKA T288, p53, p73, MYC, HDM2, and cleaved caspase 3.
V. To perform quantitative real time-polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) on post-treatment specimens for AURKA oncogenic targets: p53-regulated apoptosis inducing protein 1 (p53AIP1), VEGF, HDM2, and MYC.
OUTLINE: This is a dose-escalation study of alisertib.
Patients receive alisertib orally (PO) twice daily (BID) on days 1-3 and mFOLFOX regimen comprising oxaliplatin intravenously (IV) over 2 hours on day 2, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV continuously over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
I. To determine the maximum tolerated doses and the recommended phase II doses of modified fluorouracil, leucovorin calcium, oxaliplatin (mFOLFOX) given in combination with alisertib (MLN8237) in patients with gastrointestinal cancers.
SECONDARY OBJECTIVES:
I. To describe any anti-tumor activity associated with this treatment. II. To assess baseline tumor expression by immunohistochemistry of aurora kinase A (AURKA), v-akt murine thymoma viral oncogene homolog 1 (AKT), phosphorylated (phospho)-AKT (serine \[Ser\]473), tumor protein p53 (p53), tumor protein p73 (p73), beta (b)-catenin, v-myc myelocytomatosis viral oncogene homolog (avian) (c-MYC), and cleaved caspase 3.
III. To assess baseline messenger ribonucleic acid (mRNA) expression of AURKA, vascular endothelial growth factor (VEGF), c-MYC, human double minute 2 (HDM2), and cyclin D1 (CCND1), and correlate with response to therapy.
IV. To obtain post-treatment biopsy specimens and confirm target inhibition by assaying for AURKA, phosphorylated (p)AURKA T288, p53, p73, MYC, HDM2, and cleaved caspase 3.
V. To perform quantitative real time-polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) on post-treatment specimens for AURKA oncogenic targets: p53-regulated apoptosis inducing protein 1 (p53AIP1), VEGF, HDM2, and MYC.
OUTLINE: This is a dose-escalation study of alisertib.
Patients receive alisertib orally (PO) twice daily (BID) on days 1-3 and mFOLFOX regimen comprising oxaliplatin intravenously (IV) over 2 hours on day 2, leucovorin calcium IV over 2 hours on day 2, and fluorouracil IV continuously over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
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-2014-02475 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| VICC GI1536 | None | None | View | |
| 9824 | OTHER | Yale University Cancer Center LAO | View | |
| 9824 | OTHER | CTEP | View | |
| P30CA016359 | NIH | None | https://reporter.nih.gov/quic… | View |
| R01CA131225 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186689 | NIH | None | https://reporter.nih.gov/quic… | View |