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

NCT02860000 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: MC1431NCI-2016-01211R01CA21489315-000340
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 8

Brief 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. 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.

Conditions

Estrogen Receptor Status; HER2/Neu Negative; Invasive Breast Carcinoma; Postmenopausal; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (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

  Up to 4.5 years

Secondary Outcomes (8)

• Biomarkers and ER Alpha Expression Assessed Using Tumor Tissue

  Up to 4 weeks

• Change in Blood Biomarker Levels

  Baseline to 28 days

• Change in Tumor Biomarker Levels

  Baseline to 28 days

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

  At 24 weeks

• 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

  Up to about 5 years

Study Arms (2)

Arm I (alisertib)

EXPERIMENTAL

Patients 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.

Drug: Alisertib; Other: Laboratory Biomarker Analysis

Arm II (alisertib, fulvestrant)

EXPERIMENTAL

Patients 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.

Drug: Alisertib; Drug: Fulvestrant; Other: Laboratory Biomarker Analysis

Interventions

Alisertib DRUG

Given PO

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

Arm I (alisertib); Arm II (alisertib, fulvestrant)

Fulvestrant DRUG

Given IM

Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ZD9238

Arm II (alisertib, fulvestrant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (alisertib); Arm II (alisertib, fulvestrant)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• Any of the following therapies prior to registration:
• Chemotherapy =\< 21 days
• Immunotherapy =\< 21 days
• Biologic therapy =\< 21 days
• Hormonal therapy =\< 14 days
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Related Publications (1)

• 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.

  PMID: 36892847 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MLN 8237; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr Tufia C Haddad
• Organization: Mayo Clinic

Haddad.Tufia@mayo.edu

507-284-2511

Study Officials

• Tufia C. Haddad, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 9, 2016
• Study Start: July 6, 2017
• Primary Completion: January 10, 2022
• Study Completion: February 14, 2025
• Last Updated: February 27, 2026
• Results First Posted: October 18, 2024

Record last verified: 2026-02

Locations

US (8)