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Estrogen Receptor StatusPhase 2NCT02860000

Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer

A Phase 2 study testing Alisertib, Fulvestrant and Laboratory Biomarker Analysis in people with Estrogen Receptor Status and HER2/Neu Negative, run by Mayo Clinic at 8 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 II trial studies how well alisertib with or without fulvestrant works in treating patients with endocrine-resistant breast cancer that has spread to other places in the body. 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, women only
What is being tested?
Alisertib, Fulvestrant and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
8 sitesUnited States
Study dates
6 Jul 2017to 14 Feb 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-REGISTRATION ELIGIBILITY
  • Post-menopausal defined as
  • Age >= 60 and amenorrhea > 12 consecutive months, OR
  • Age < 60 and amenorrhea > 12 consecutive months without another cause and documented follicle stimulating hormone (FSH) level of > 35 mIU/mL, OR
  • Previous bilateral oophorectomy
  • Histologic proof of metastatic or locally advanced, unresectable breast cancer
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  • History of ER positive (+) (>= 10% of cells positive on hematoxylin and eosin stain [H\&E]), HER2 negative (-) breast cancer disease, either as a
  • History of primary, operable ER+/HER2- invasive breast cancer OR
  • History of de novo metastatic breast cancer that is ER+/HER2-
  • Note: HER2- (negative) disease defined as one of the following:
  • HER2 immunohistochemistry (IHC) expression of 0, 1+ and in-situ hybridization (ISH) non-amplified
  • HER2 IHC expression of 0, 1+ and ISH not done
  • HER2 IHC expression of 2+ and ISH non-amplified
  • IHC not done and ISH non-amplified
  • Prior treatment
  • No more than two prior chemotherapy regimens in the metastatic setting
  • Prior treatment with fulvestrant in the metastatic setting is required, except for patients with a history of ER-negative metastatic breast cancer
  • Unlimited prior endocrine therapy regimens in the metastatic setting are allowed
  • No prior treatment with an aurora Kinase inhibitor (either an aurora A or pan-aurora kinase inhibitor)
  • Disease that is measurable where:
  • A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
  • A malignant lymph node is considered measurable if its short axis is >= 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm); Note: tumor lesions in a previously irradiated area are not considered measurable disease; Note: disease that is measurable by physical examination only is not eligible
  • No history of tumors involving spinal cord or heart
  • History of brain metastases as per the following criteria:
  • Patients with a history of resected brain metastases are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including < 28 days prior to pre-registration
  • Patients who receive stereotactic radiosurgery or whole brain radiation for brain metastases are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including < 28 days prior to pre-registration
  • Fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment;
  • EXCEPTION: neuropathies - if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1, 2
  • Not receiving administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes
  • Willing to limit daily alcohol intake to the following: one 12-oz glass of beer, one 6-oz glass of wine, or one 1.5-oz portion of 80-proof alcohol
  • No uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Uncontrolled symptomatic cardiac arrhythmia
  • Uncontrolled hypertension (defined as blood pressure > 160/90)
  • No 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
  • No other active second malignancy other than non-melanoma skin cancers and in situ cervical cancers within 5 years of registration
  • NOTE: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 5 years prior to registration
  • Ability to provide written informed consent
  • Willing to return to enrolling institution for follow-up during the active treatment; event monitoring following completion of therapy may occur outside the enrolling institution
  • No history of myocardial infarction =< 6 months prior to pre-registration or 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
  • No prior allogeneic bone marrow or organ transplantation
  • No known clinical finding or suspicion of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
  • No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Able to swallow oral medication
  • No known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib; examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease
  • No visceral crisis: Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
  • No requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes
  • Willing to undergo a biopsy of a metastatic site of breast disease for central laboratory determination of ER and correlative research purposes
  • REGISTRATION ELIGIBILITY CRITERIA
  • =< 28 days post pre-registration
  • Central ER determination on pre-registration biopsy completed
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Alanine transaminase (ALT) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
  • Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula
  • Willing to provide blood and tissue for correlative research purposes

Who cannot join

  • REGISTRATION EXCLUSION CRITERIA
  • Any of the following therapies prior to registration:
  • Chemotherapy =< 21 days
  • Immunotherapy =< 21 days
  • Biologic therapy =< 21 days
  • Hormonal therapy =< 14 days
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  • Monoclonal antibodies =< 14 days
  • Radiation therapy =< 14 days
  • Administration of myeloid growth factors or platelet transfusion =< 14 days prior to registration
  • Systemic infection requiring intravenous (IV) antibiotic therapy =< 14 days prior to registration
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort =< 14 days prior to registration
  • Receipt of corticosteroids =< 7 days prior to registration, unless patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 30 days prior to registration

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: MC1431 Randomized Phase II Trial to Evaluate Alisertib Alone or Combined With Fulvestrant for Women With Advanced, Endocrine-Resistant Breast Cancer

This phase II trial studies how well alisertib with or without fulvestrant works in treating patients with endocrine-resistant breast cancer that has spread to other places in the body. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells or reducing the amount of estrogen made by the body. Giving alisertib with or without fulvestrant may be better in treating patients with breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the impact on objective tumor response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria) with the addition of fulvestrant to alisertib in women with endocrine resistant, advanced estrogen receptor positive breast cancer.

SECONDARY OBJECTIVES:

  1. To evaluate the safety profile of each treatment regimen. II. To assess the impact on median progression-free survival with the addition of fulvestrant to alisertib.

III. To obtain estimated tumor response rate and the median progression-free survival time during alisertib and fulvestrant treatment in the cohort of patients who progress during alisertib monotherapy, and crossover to receive the combination of alisertib and fulvestrant.

TERTIARY OBJECTIVES:

  1. To assess the changes in aurora A kinase, SMAD5 and SOX2 expression and phosphorylation in tumor tissue after first cycle of assigned treatment.

II. To assess the changes in estrogen receptor (ER) expression and function in tumor tissue after the first cycle of assigned treatment.

III. To generate patient derived xenografts (PDX) from tumors collected at baseline and progression of disease (PD) in order to identify mechanisms associated with both de novo and acquired alisertib resistance.

IV. After the first cycle of treatment, to assess changes in aurora A kinase, phosphorylated (p)~SOX2 and ER expression on circulating tumor cells (CTCs), and to assess concordance between change in expression with tumor tissue and CTCs.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive alisertib orally (PO) twice daily (BID) on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.

ARM II: Patients receive fulvestrant intramuscularly (IM) over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Being tested
Alisertib, Fulvestrant, Laboratory Biomarker Analysis
Medical subject headings
Breast 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

  • FulvestrantDrug

    Also called Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780

    Given IM

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02860000
Study groupRoleWhat they receive
Arm I (alisertib)ExperimentalPatients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis
Arm II (alisertib, fulvestrant)ExperimentalPatients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Alisertib; Drug: Fulvestrant; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Tumor Response Rate Defined as 100% Times the Number of Patients Who Meet the Criteria for Complete Response (CR) or Partial Response (PR) Using RECIST Criteria Version 1.1

    For arm I, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with alisertib monotherapy divided by the number of patients who started alisertib monotherapy. For arm II, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with combination of alisertib and fulvestrant divided by the number of patients who started treatment with the combination of a

    Measured: Up to 4.5 years

Secondary outcomes (8)

  1. Biomarkers and ER Alpha Expression Assessed Using Tumor Tissue

    Spearman rank correlation coefficient will be used to examine the association between ER alpha expression and the biomarkers: CD44, CD24, total and phosphorylated expression of AURKA, SMAD5, and SOX2. A two sample test of the difference in proportions will be used to examine whether weak or no phosphorylated expression of AURKA, SMAD5, and SOX2 after one cycle of alisertib is associated with clinical benefit (CR + PR + stable disease on treatment for at least 6 months).

    Measured: Up to 4 weeks

  2. Change in Blood Biomarker Levels

    Percent change in CTC expression of aurora A kinase, ER, and phospho- SOX2 expression from pre-treatment levels will be determined for each patient. Bland-Altman plots and weighted kappa statistics will be used to examine the concordance between the percent change in aurora A kinase, ER, and phospho-SOX2 expression from pre-treatment levels in CTC and in tumor tissue.

    Measured: Baseline to 28 days

  3. Change in Tumor Biomarker Levels

    Spearman rank correlation coefficient will be used to examine the association of maximum percentage of tumor shrinkage during treatment with the percent change after 1 cycle of treatment in aurora A Kinase (AAK) expressing cells, as well as percent changes after 1 cycle of treatment in tissue ER alpha, SMAD5, SOX2 expression and phosphorylation.

    Measured: Baseline to 28 days

  4. Clinical Benefit Rate (CBR) During Initial Treatment Defined as Percentage of Patients Who Completed 6 Courses of Treatment Without Documentation of Disease Progression

    For initial treatment in each arm, the CBR at 24 weeks will be defined as the proportion of patients who completed 6 cycles of treatment without documentation of disease progression.

    Measured: At 24 weeks

  5. Duration of Response

    Defined as time from randomization to disease progression among those patients whose disease meets the RECIST criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during initial treatment

    Measured: Up to about 5 years

  6. Incidence of Grade 4 Adverse Events Graded by Common Terminology Criteria-Criteria for Adverse Events (CTCAE) Version 4.0

    The CTCAE version 4.0 will be used to grade and assign attribution to each adverse event reported during initial treatment and crossover treatment separately.

    Measured: Up to 30 days after last administration of study drug

  7. Overall Survival

    Will be estimated using the Kaplan-Meier method.

    Measured: Up to 5 years

  8. Progression-free Survival

    Defined as time from randomization to the first of these disease events: local/regional or distant breast recurrence, DCIS or invasive breast disease in contralateral breast, non-breast second primary, or death due to any cause

    Measured: Up to 5 years

Timeline

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

  1. First posted9 Aug 2016 (estimated)
  2. Study start6 Jul 2017
  3. Primary completion10 Jan 2022
  4. Study completion14 Feb 2025

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02860000
Sponsor's protocol ID
MC1431
Other IDs
R01CA214893, 15-000340
Status last verified
Aug 2026
First submitted
4 Aug 2016
Last updated
24 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Haddad TC, Suman VJ, D'Assoro AB, Carter JM, Giridhar KV, McMenomy BP, Santo K, Mayer EL, Karuturi MS, Morikawa A, Marcom PK, Isaacs CJ, Oh SY, Clark AS, Mayer IA, Keyomarsi K, Hobday TJ, Peethambaram PP, O'Sullivan CC, Leon-Ferre RA, Liu MC, Ingle JN, Goetz MP. Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 TBCRC041 Randomized Clinical Trial. JAMA Oncol. 2023 Jun 1;9(6):815-824. doi: 10.1001/jamaoncol.2022.7949.

    PubMed 36892847

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alisertib, Fulvestrant and Laboratory Biomarker Analysis in people with Estrogen Receptor Status and HER2/Neu Negative, run by Mayo Clinic at 8 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 61 inclusion and 12 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 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Tumor Response Rate Defined as 100% Times the Number of Patients Who Meet the Criteria for Complete Response (CR) or Partial Response (PR) Using RECIST Criteria Version 1.1 (time frame: Up to 4.5 years). 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 NCT02860000, 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 24 Sep 2026.

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