Alisertib and Fulvestrant in Treating Patients With Hormone Receptor Positive Breast Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

NCT02219789 | Completed Phase 1 DMC

• 3 other identifiers: MC1231NCI-2014-01726P30CA015083
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of alisertib when given together with fulvestrant in treating patients with hormone positive breast cancer that has spread to other parts of the body or has spread from where it started to nearby tissue or lymph nodes and cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are type of hormones made by the body and they can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen or progesterone the body makes. Giving alisertib together with fulvestrant may be a better treatment for breast cancer.

Conditions

Estrogen Receptor Positive; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of alisertib in combination with fulvestrant graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  The MTD is defined as the highest dose level among those under consideration where at most 1 of 6 patients develops a dose limiting toxicity and 2 or more of the 3-6 patients treated at the next higher dose level develop a dose limiting toxicity. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

  28 days

Secondary Outcomes (1)

• Tumor response (complete or partial response) using Response Evaluation Criteria in Solid Tumors version 1.1

  Up to 1 month post-treatment

Other Outcomes (2)

• Aurora A kinase (AURKA) expression levels

  Baseline

• Expression levels of ER-alpha, SMAD family member 5 (P~SMAD5), (sex determining region Y)-box 2 (SOX-2), E-cadherin, vimentin, cluster of differentiation (CD)44, CD24, and protein C receptor, endothelial (PROCR)

  Up to 1 month post-treatment

Study Arms (1)

Treatment (alisertib, fulvestrant)

EXPERIMENTAL

Patients receive fulvestrant IM on day 1 (days 1 and 15 of course 1 only) and 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

Treatment (alisertib, fulvestrant)

Fulvestrant DRUG

Given IM

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

Treatment (alisertib, fulvestrant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib, fulvestrant)

Eligibility Criteria

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

You may qualify if:

• Histologic proof of metastatic or locally advanced, unresectable breast cancer which is estrogen receptor positive and/or progesterone positive per institutional standards
• Non-measurable or measurable disease
• Post-menopausal women, as verified by:
• Post bilateral surgical oophorectomy, or
• No spontaneous menses \>= 1 year, or
• No menses for \< 1 year with follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range, according to institutional standards
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet (PLT) \>= 100,000/mm\^3
• Total bilirubin =\< 1.5 upper limit of normal (ULN)
• Alanine transaminase (ALT) =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement)
• Creatinine =\< 1.5 x ULN
• Hemoglobin \>= 9.0 gm/dL
• Calculated creatinine clearance must be \>= 45 ml/min using the Cockcroft-Gault formula
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Ability to provide informed written consent

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• 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
• Any of the following prior therapies:
• Chemotherapy =\< 21 days prior to registration
• Mitomycin C/nitrosoureas =\< 42 days prior to registration
• Immunotherapy =\< 28 days prior to registration
• Biologic therapy =\< 28 days prior to registration
• Radiation therapy =\< 21 days prior to registration
• Radiation to \> 25% of bone marrow prior to registration
• Hormonal therapy =\< 14 days prior to registration
• Failure to recover to grade =\< 1 from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
• Uncontrolled central nervous system (CNS) metastases
• NOTE: metastases have been treated by surgery and/or radiotherapy and patients have been neurologically stable and off of steroids \> 12 weeks are eligible
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation)
• 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

Sponsors & Collaborators

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

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

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

Study Officials

• Tufia Haddad

  Mayo Clinic

  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 15, 2014
• First Posted: August 19, 2014
• Study Start: December 5, 2014
• Primary Completion: March 28, 2016
• Study Completion: October 1, 2018
• Last Updated: October 3, 2018

Record last verified: 2018-10

Locations

US (1)