Alisertib and Combination Chemotherapy in Treating Patients With Gastrointestinal Tumors
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|ClinicalTrials.gov Identifier: NCT02319018|
Recruitment Status : Completed
First Posted : December 18, 2014
Last Update Posted : October 8, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malignant Digestive System Neoplasm||Drug: Alisertib Drug: Fluorouracil Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Oxaliplatin||Phase 1|
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.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Alisertib (MLN8237) in Combination With mFOLFOX in Gastrointestinal Tumors|
|Actual Study Start Date :||August 27, 2015|
|Actual Primary Completion Date :||September 29, 2018|
|Actual Study Completion Date :||September 29, 2018|
Experimental: Treatment (alisertib, mFOLFOX)
Patients receive alisertib PO BID on days 1-3 and mFOLFOX regimen comprising oxaliplatin 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.
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
- Maximum tolerated dose and the recommended phase II doses of mFOLFOX given in combination with alisertib, defined as the dose level at which the probability of dose limiting toxicities is 30% [ Time Frame: 28 days ]
- Anti-tumor activity associated with this treatment, evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 weeks after last dose of study drugs ]
- Tumor expression by immunohistochemistry [ Time Frame: Up to 4 weeks after last dose of study drugs ]Exploratory analyses to assess the correlation of response with the biomarkers will also be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02319018
|United States, Connecticut|
|Smilow Cancer Center/Yale-New Haven Hospital|
|New Haven, Connecticut, United States, 06510|
|New Haven, Connecticut, United States, 06520|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Laura Goff||Yale University Cancer Center LAO|