Alisertib and Combination Chemotherapy in Treating Patients With Gastrointestinal Tumors

NCT02319018 | Completed Phase 1 DMC

• 6 other identifiers: NCI-2014-02475VICC GI15369824P30CA016359R01CA131225UM1CA186689
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

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.

Conditions

Malignant Digestive System Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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%

  28 days

Secondary Outcomes (1)

• 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

  Up to 4 weeks after last dose of study drugs

Other Outcomes (1)

• Tumor expression by immunohistochemistry

  Up to 4 weeks after last dose of study drugs

Study Arms (1)

Treatment (alisertib, mFOLFOX)

EXPERIMENTAL

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.

Drug: Alisertib; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin

Interventions

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

Treatment (alisertib, mFOLFOX)

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (alisertib, mFOLFOX)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib, mFOLFOX)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (alisertib, mFOLFOX)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (alisertib, mFOLFOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed gastrointestinal malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom FOLFOX would be an appropriate therapy
• Patients are required to have evaluable disease
• Any number of prior treatment regimens is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin below institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 3 x institutional upper limit of normal
• Creatinine below institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of MLN8237 (alisertib) administration; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN8237 administration
• Ability to understand and the willingness to sign a written informed consent document
• Patients must be able to take oral medications

You may not qualify if:

• Patients who have had targeted therapy, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines, 5-FU (fluorouracil), leucovorin (leucovorin calcium) or oxaliplatin
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN8327
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Prior allogeneic bone marrow or organ transplantation
• Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
• Requirement for constant administration of proton pump inhibitor, histamine (H2) antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed as described
• Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel
• Patients requiring any medications or substances that are strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or clinically significant enzyme inducers of CYP3A4 are ineligible
• Patients with grade 2 peripheral neuropathy or greater are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

MLN 8237; Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Laura Goff

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 18, 2014
• Study Start: August 27, 2015
• Primary Completion: September 29, 2018
• Study Completion: September 29, 2018
• Last Updated: October 9, 2018

Record last verified: 2018-10

Locations

US (5)