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Malignant Digestive System NeoplasmPhase 1NCT02319018

Alisertib and Combination Chemotherapy in Treating Patients With Gastrointestinal Tumors

A Phase 1 study testing Alisertib, Fluorouracil and Laboratory Biomarker Analysis in people with Malignant Digestive System Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Digestive System Neoplasm
What is being tested?
Alisertib, Fluorouracil and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
5 sitesUnited States
Study dates
27 Aug 2015to 29 Sep 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: A Phase 1 Study of Alisertib (MLN8237) in Combination With mFOLFOX in Gastrointestinal Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Alisertib, Fluorouracil, Laboratory Biomarker Analysis, Leucovorin Calcium, Oxaliplatin
Medical subject headings
Gastrointestinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlisertibDrug

    Also called Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

    Given PO

  • FluorouracilDrug

    Also called 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

Study groups in NCT02319018
Study groupRoleWhat they receive
Treatment (alisertib, mFOLFOX)ExperimentalPatients 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.
Receives: Drug: Alisertib; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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%

    Measured: 28 days

Secondary outcomes (1)

  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

    Measured: Up to 4 weeks after last dose of study drugs

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2014 (estimated)
  2. Study start27 Aug 2015
  3. Primary completion29 Sep 2018
  4. Study completion29 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02319018
Sponsor's protocol ID
NCI-2014-02475
Other IDs
NCI-2014-02475, VICC GI1536, 9824, 9824, P30CA016359, R01CA131225, UM1CA186689
Status last verified
Oct 2018
First submitted
17 Dec 2014
Last updated
9 Oct 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alisertib, Fluorouracil and Laboratory Biomarker Analysis in people with Malignant Digestive System Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02319018.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2018.

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