Tamoxifen Citrate, Anastrozole, or Fulvestrant in Treating Patients with Stage I-III Invasive Lobular Breast Cancer

Status: Active

Description

This phase II trial studies how well tamoxifen citrate, anastrozole, or fulvestrant work in treating patients with stage I-III invasive lobular breast cancer. Tamoxifen citrate and anastrozole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tamoxifen citrate, anastrozole, or fulvestrant will work better in treating patients with invasive lobular breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed invasive lobular breast cancer, that is hormone receptor-positive and HER2-negative, measuring at least 1 centimeter (cm) radiographically or clinically, clinical stages I-III; invasive lobular histology will be diagnosed at the enrolling institution for purposes of study participation; subsequently, invasive lobular histology will be confirmed by central pathology review, but this central review will not be required prior to patient enrollment
  • Prior to initiation of study agents, study participants will be highly encouraged to undergo a baseline research core biopsy of their breast tumor; if this is not possible or the patient refuses, the pre-treatment tumor sample must be obtained from their archival diagnostic core biopsy; if definitive surgery is not performed at day 21-27 after study treatment, a second post-treatment research core biopsy will need to be obtained from their breast tumor; for patients undergoing surgery, the second biopsy will be removed from the breast tumor tissue excised during their operation; Note: In the event that the baseline breast tumor biopsy performed for research purposes does not yield adequate tumor tissue for analysis of the primary and secondary endpoints, tissue will be requested from the patient's archival clinical diagnostic core biopsy if it is available; the patient will still remain on study and complete protocol therapy as planned in this unlikely event
  • Hormone receptor (HR) status of the invasive component must be documented before trial enrollment; the tumor must be HR-positive; HR will be considered positive if staining is 1% or greater for ER and/or PR; this will be determined at the enrolling institution for purposes of study participation and enrollment onto the trial; subsequently, HR status will be confirmed by central pathology review, but this central review will not be required prior to enrolling the patient; HER2 status will be determined locally only, based upon current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
  • Participants must be fully postmenopausal
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Leukocytes >= 3,000/mm^3
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin within normal laboratory limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the laboratory upper limit of normal
  • Creatinine within normal laboratory limits
  • Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin), but must have been discontinued at least 30 days prior to the study enrollment; vaginal preparations (e.g., Vagifem or Estring) are allowed
  • Participant must be aware of the nature of her malignancy, understand the study requirements and risks and be able and willing to sign a written informed consent document

Exclusion Criteria

  • Prior or concurrent use of hormonal therapy, chemotherapy, radiation therapy, or novel therapy to treat the current breast cancer, including any history of prior irradiation to the ipsilateral breast; additionally, the patient must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 2 years prior to study enrollment; Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the 21 day study intervention period
  • Concurrent use of any other investigational agents
  • History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to tamoxifen, anastrozole, or fulvestrant or any of their ingredients
  • History of thromboembolic disease or uterine cancer that is considered a contraindication to tamoxifen
  • Active hepatitis viral infections
  • Uncontrolled current 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
  • HER-2 positivity

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Erica M. Stringer-Reasor
Phone: 205-934-2992
Email: strinem@uab.edu

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Rita Mukhtar
Email: Rita.Mukhtar@ucsf.edu

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Rita Nanda
Phone: 773-834-2756
Email: rnanda@medicine.bsd.uchicago.edu

Minnesota

Rochester
Mayo Clinic
Status: Active
Contact: Kim Hitchcock
Phone: 507-538-1397
Email: hitchcock.kimberly@mayo.edu

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Joseph Anthony Sparano
Phone: 718-405-8404

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Kristalyn K Gallagher
Phone: 919-966-5221
Email: kristalyn_gallagher@med.unc.edu

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Rachel C. Jankowitz
Phone: 412-641-6500
Email: jankowitzr@upmc.edu

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Julie Rani Nangia
Email: nangia@bcm.edu
M D Anderson Cancer Center
Status: Active
Contact: Isabelle Bedrosian
Phone: 713-563-1872
Email: ibedrosian@mdanderson.org

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Contact: Hannah Margaret Linden
Phone: 206-288-6710
Email: hmlinden@u.washington.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the change from baseline to post-treatment Ki67 values in hormone receptor (HR)-positive, HER2-negative invasive lobular carcinoma (ILC) tissue derived from postmenopausal women awaiting definitive surgery or further neoadjuvant treatment who are randomized to 21-27 days of neoadjuvant endocrine treatments with fulvestrant (two 250 mg intramuscular [IM] injections given on day 1 and 15), anastrozole (1 mg given orally daily), or tamoxifen citrate (tamoxifen) (20 mg given orally daily).

SECONDARY OBJECTIVES:

I. To compare between arms Ki67 values following neoadjuvant therapy.

II. To evaluate estrogen receptor (ER) protein expression in ILC tissues at baseline and following neoadjuvant endocrine therapy.

III. To evaluate progesterone receptor (PR) protein expression in ILC tissues at baseline and following neo-adjuvant endocrine therapy.

IV. To evaluate ER-related and ILC-specific candidate gene messenger ribonucleic acid (mRNA) expression in ILC tissues at baseline and following neoadjuvant endocrine therapy in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance in ILC.

V. To evaluate associations between changes in Ki67 in ILC tissues following neoadjuvant endocrine therapy with ER and PR protein expression, or ER and candidate gene mRNA expression at baseline and post-treatment.

TERTIARY OBJECTIVES:

I. To evaluate deoxyribonucleic acid (DNA) methylation in ILC tissues at baseline and following neoadjuvant endocrine therapy.

II. To evaluate associations between germline and somatic DNA sequence variants with changes in Ki67 in ILC tissues following neoadjuvant endocrine therapy.

III. To evaluate the activity of signaling pathways in ILC tissues by immunohistochemical or other protein analyses, such as histone modifications, at baseline and following neoadjuvant endocrine therapy.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive fulvestrant IM on days 1 and 15 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive anastrozole orally (PO) once daily (QD) for 21-27 days in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive tamoxifen citrate PO QD for 21-27 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Rachel C. Jankowitz

Trial IDs

Primary ID 13-164
Secondary IDs NCI-2018-00191, TBCRC037
Clinicaltrials.gov ID NCT02206984