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Mucinous Adenocarcinoma of the ColonPhase 1NCT01923337

Irinotecan and Alisertib in Treating Patients With Advanced Solid Tumors or Colorectal Cancer

A Phase 1 study testing irinotecan hydrochloride and alisertib in people with Mucinous Adenocarcinoma of the Colon and Mucinous Adenocarcinoma of the Rectum, run by University of California, Davis at 1 site 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 irinotecan hydrochloride in treating patients with advanced solid tumors or colorectal cancer. Irinotecan hydrochloride and 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
What is being tested?
irinotecan hydrochloride and alisertib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Aug 2013to 17 Oct 2016
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

  • Eligibility for dose escalation cohort: Histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective OR solid tumor for which irinotecan monotherapy is considered standard
  • Eligibility for the expansion cohort: Histologically or cytologically confirmed colon or rectal adenocarcinoma for which curative treatment does not exist; patients must have documented progression or intolerance to at least one prior regimen containing 5-fluorouracil or capecitabine and oxaliplatin
  • Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status 0 - 2
  • Patients may have measurable or non-measurable disease; x-rays and/or scans for disease assessment of measurable disease must have been completed within 28 days prior to registration; non-measurable disease must also be assessed within 28 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500/mm3
  • Platelet count >= 100,000/mm3
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  • Total bilirubin within institutional normal limits
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 times institutional upper limit of normal or =< 5.0 times institutional upper limit of normal in the presence of liver metastases
  • Creatinine =< 1.5 times institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 measured by 24-hour urine collection
  • Any number of prior chemotherapy regimens is allowed
  • Any prior chemotherapy, immunotherapy or targeted therapy must have been completed at least 4 weeks prior to start of this protocol and all side effects (except alopecia, lymphopenia and hyperglycemia) resolved to grade 1 or less; any prior radiation must have been completed at least 2 weeks prior to start of therapy
  • Pregnant or nursing women are ineligible because of the risk to the fetus; 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 and for the duration of study participation
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to swallow and retain oral medications
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • Male subject agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of MLN8237; male patients, even if surgically sterilized (i.e., status postvasectomy) must agree to practice effective barrier contraception during the entire study treatment period and through four months after the last dose of study drug, or completely abstain from heterosexual intercourse
  • Subject must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration

Who cannot join

  • Prior treatment with irinotecan or aurora A-targeted agents, including MLN8237
  • A history of known Gilbert's syndrome or homozygous presence of the uridine diphosphate (UDP)-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele on pre-treatment testing
  • Symptomatic or uncontrolled brain metastasis; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis; previously treated brain metastases will be allowed as long as the patient is neurologically stable and is off steroids and anticonvulsants at the time of registration
  • Prior radiation to greater than 25% of the bone marrow or whole pelvis radiation
  • Patients requiring full therapeutic anticoagulation including warfarin, heparin, low-molecular weight heparin, or direct factor Xa inhibitor are ineligible because therapy on this trial may result in frequent and recurrent thrombocytopenia; patients requiring prophylactic dose anticoagulation may be eligible after discussion with the principal investigator
  • Patients with a diagnosis of active human immunodeficiency virus (HIV) infection, on anti-retroviral therapy, or with a cluster of differentiation (CD)4 count less than 200 are ineligible due to potential interactions between irinotecan and anti-retroviral medications as well as possible immunosuppressive activity of the study treatment; testing is not required in the absence of clinical findings or suspicion
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  • Patients with a diagnosis of chronic hepatitis B are ineligible due to the possibility of immunosuppression on study treatment
  • Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
  • Patients may not take known strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers such as phenytoin, carbamazepine, phenobarbital, rifampin or St. John's wort or strong CYP3A4 inhibitors such as ketoconazole, diltiazem, or verapamil
  • Known or suspected allergy to irinotecan or MLN8237, or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills; patients with feeding tubes, intractable nausea or vomiting, or a malabsorption syndrome are not eligible
  • Any clinically significant medical or psychiatric condition that would interfere with protocol treatment
  • Prior allogeneic bone marrow or organ transplantation
  • Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment
  • 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
  • Requirement for constant administration of proton pump inhibitors, H2 antagonists, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  • Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patient has received other investigational drugs with 14 days before enrollment
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I Study of the Combination of Irinotecan and MLN8237 in Advanced Solid Tumors With Emphasis on Colorectal Cancer

This phase I trial studies the side effects and best dose of alisertib when given together with irinotecan hydrochloride in treating patients with advanced solid tumors or colorectal cancer. Irinotecan hydrochloride and alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the feasibility and safety of MLN8237 (alisertib) when given in combination with irinotecan (irinotecan hydrochloride) to patients with advanced solid tumors.

SECONDARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of MLN8237 when given in combination with irinotecan to patients with advanced solid tumors and to recommend a phase II dose for the combination.

II. To obtain preliminary evidence of efficacy for this combination. III. To compare the pharmacokinetics of SN-38 (the active metabolite of irinotecan) with and without concurrent administration of MLN8237 in an expanded cohort of patients with advanced colorectal cancer.

OUTLINE: This is a dose-escalation study of alisertib.

Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and alisertib orally (PO) twice daily (BID) on days 1-3 and 8-10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
irinotecan hydrochloride, alisertib
Keywords
Colorectal cancer
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Colorectal Neoplasms

What participants receive

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

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • alisertibDrug

    Also called Aurora A kinase inhibitor MLN8237, MLN8237

    Given PO

Study groups in NCT01923337
Study groupRoleWhat they receive
Treatment (irinotecan, alisertib)ExperimentalPatients receive irinotecan hydrochloride IV over 30 minutes on days 1 and 8 and alisertib PO BID on days 1-3 and 8-10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: irinotecan hydrochloride; Drug: alisertib

What is being measured

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

  1. MTD, defined as the highest dose tested in which fewer than 33% of patients experience dose-limiting toxicity (DLT) attributable to the study drugs, graded using the National Cancer Institute (NCI) CTCAE version 4.0

    Measured: Up to day 21

Secondary outcomes (4)

  1. Incidence of toxicities observed at each dose level graded according to NCI CTCAE version 4.0

    Will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by grade and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility of outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

    Measured: Up to 30 days

  2. Response rates, as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Measured: Up to 30 days

  3. Survival

    Summarized with Kaplan-Meier plots.

    Measured: Up to 30 days

  4. Time to failure

    Summarized with Kaplan-Meier plots.

    Measured: Up to 30 days

Timeline

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

  1. First posted15 Aug 2013 (estimated)
  2. Study startAug 2013
  3. Primary completion17 Oct 2016
  4. Study completion17 Oct 2016

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01923337
Sponsor's protocol ID
440954
Other IDs
UCDCC#234, UCDCC#234, P30CA093373, X14013, NCI-2013-01387
Status last verified
Jan 2019
First submitted
13 Aug 2013
Last updated
4 Jan 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Semrad TJ, Kim EJ, Gong IY, Li T, Christensen S, Arora M, Riess JW, Gandara DR, Kelly K. Phase 1 study of alisertib (MLN8237) and weekly irinotecan in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2021 Aug;88(2):335-341. doi: 10.1007/s00280-021-04293-3. Epub 2021 May 15.

    PubMed 33993383

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing irinotecan hydrochloride and alisertib in people with Mucinous Adenocarcinoma of the Colon and Mucinous Adenocarcinoma of the Rectum, run by University of California, Davis at 1 site 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 18 inclusion and 22 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 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

MTD, defined as the highest dose tested in which fewer than 33% of patients experience dose-limiting toxicity (DLT) attributable to the study drugs, graded using the National Cancer Institute (NCI) CTCAE version 4.0 (time frame: Up to day 21). 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 NCT01923337, which also lists 1 linked publication.

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 4 Jan 2019.

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