NCT01923337

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2013

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2013

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

August 13, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 15, 2013

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 17, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 17, 2016

Completed
Last Updated

January 4, 2019

Status Verified

January 1, 2019

Enrollment Period

3.2 years

First QC Date

August 13, 2013

Last Update Submit

January 2, 2019

Conditions

Mucinous Adenocarcinoma of the ColonMucinous Adenocarcinoma of the RectumRecurrent Colon CancerRecurrent Rectal CancerSignet Ring Adenocarcinoma of the ColonSignet Ring Adenocarcinoma of the RectumStage IIIA Colon CancerUnspecified Adult Solid Tumor, Protocol Specific

Keywords

Colorectal cancer

Outcome Measures

Primary Outcomes (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

    Up to day 21

Secondary Outcomes (4)

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

    Up to 30 days

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

    Up to 30 days

  • Survival

    Up to 30 days

  • Time to failure

    Up to 30 days

Study Arms (1)

Treatment (irinotecan, alisertib)

EXPERIMENTAL

Patients 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.

Drug: irinotecan hydrochlorideDrug: alisertib

Interventions

irinotecan hydrochlorideDRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E
Treatment (irinotecan, alisertib)
alisertibDRUG

Given PO

Also known as: Aurora A kinase inhibitor MLN8237, MLN8237
Treatment (irinotecan, alisertib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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
  • +3 more criteria

You may not qualify if:

  • 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
  • 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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

  • 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.

    PMID: 33993383DERIVED

Related Links

MeSH Terms

Conditions

Colonic NeoplasmsRectal NeoplasmsColorectal Neoplasms

Interventions

IrinotecanMLN 8237

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Study Officials

  • Thomas Semrad

    UC Davis Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

August 13, 2013

First Posted

August 15, 2013

Study Start

August 1, 2013

Primary Completion

October 17, 2016

Study Completion

October 17, 2016

Last Updated

January 4, 2019

Record last verified: 2019-01

Locations

US(1)