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Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03219476
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : March 8, 2019
Information provided by (Responsible Party):
Lubna Chaudhary, Medical College of Wisconsin

Brief Summary:
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.

Condition or disease Intervention/treatment Phase
Breast Cancer Invasive Breast Cancer Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Tamoxifen Phase 2

Detailed Description:

STUDY RATIONALE: Patients with HR+ HER2- node-negative breast cancers generally undergo surgical resection upfront, followed by adjuvant chemotherapy, if needed, in addition to adjuvant endocrine therapy. Because endocrine therapy is primarily delivered in the postoperative setting, the ability to assess the tumor response to this treatment modality is lost and very difficult to assess. This study offers the unique opportunity to assess the responsiveness of breast tumors to endocrine therapy while the tumors are still in vivo by treating patients with endocrine therapy before surgery and assessing molecular changes with treatment. By comparing pre- and post-treatment levels of molecular markers in individual tumors, the team expects to identify predictors of responsiveness to existing agents and identify new candidate therapeutic targets.

PRIMARY OBJECTIVE: The primary objective is to determine the frequency of increased HER family of receptor tyrosine kinases protein expression in tumors, following treatment with neoadjuvant endocrine therapy and their correlation with Ki-67 tumor responses. The team will measure cancer cell protein levels of growth factor receptors of the HER family before and after neoadjuvant endocrine therapy. The data will be used to inform a future randomized trial of combined endocrine and the most promising anti-HER targeted therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
Actual Study Start Date : February 5, 2017
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. Choice of endocrine therapy (aromatase inhibitors or tamoxifen) would be decided by medical oncologist, following a review of the patient's medical history and menstrual status. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
Drug: Anastrozole
1 mg once daily.

Drug: Letrozole
2.5mg once daily.

Drug: Exemestane
25 mg once daily.

Drug: Tamoxifen
20 mg once daily.

Primary Outcome Measures :
  1. Protein expression will be quantified on slides, using optimized immunohistochemical protocols for planned study biomarkers. [ Time Frame: At four weeks. ]
  2. Ki-67 assessment specimens will be assessed by manual counting of stained tumor cells. [ Time Frame: At four weeks. ]
  3. Ki-67 assessment specimens will be assessed by quantitative immunohistochemistry. [ Time Frame: At four weeks. ]
  4. Changes in tumor size will be assessed with unilateral mammogram. [ Time Frame: At four weeks. ]

Secondary Outcome Measures :
  1. Patient outcomes (e.g., distant recurrences) will be assessed by chart review in follow-up. [ Time Frame: Five years. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Females.
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female; age ≥18 years.
  • Pathologically proven diagnosis of invasive breast cancer, clinically stage I-II.
  • Clinically lymph node negative, confirmed by clinical exam and/or ultrasound imaging.
  • Estrogen- and/or progesterone-receptor-positive tumor, defined ≥1% positively staining cells by immunohistochemistry, according to the current ASCO/CAP guidelines.
  • HER2/neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
  • ECOG performance status 0-2.
  • Pretreatment evaluations (minimum diagnostic workup) within 28 days prior to study
  • Qualify for anti-endocrine treatment (per medical oncologist).
  • Informed consent provided.
  • If history of contralateral breast cancer, patient completed all treatment two years prior
  • No treatment for this breast cancer or any malignancy within two years (except non-melanomatous skin cancer, carcinoma in situ of the cervix and contralateral breast cancer)
  • Using adequate methods of contraception; negative pregnancy test.
  • No strong CYP2D6 inhibitors.
  • Adequate organ function with baseline lab values.

    • Absolute neutrophil count (ANC) ≥ 1500/µL.
    • Hemoglobin (Hb) ≥ 9g/dL.
    • Platelet count ≥ 100,000/µL.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
    • Serum bilirubin within ≤ 1.5 x ULN.

Exclusion Criteria:

  • AJCC clinical T4, N1-3 or M1, breast cancer.
  • Synchronous non-breast malignancy (exceptions include non-melanomatous skin cancer, carcinoma in situ of the cervix).
  • Purely noninvasive breast cancer (i.e., ductal carcinoma in situ, lobular carcinoma in situ).
  • Men with breast cancer.
  • Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent.
  • Pregnant or lactating women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03219476

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Contact: Medical College of Wisconsin Clinical Trials Office 414-805-8900

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United States, Wisconsin
Froedtert Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Lubna Chaudhary, MD    414-805-4600   
Contact: Medical College of Wisconsin Cancer Center Clinical Trials Office    414-805-8900   
Sponsors and Collaborators
Medical College of Wisconsin
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Principal Investigator: Lubna Chaudhary Medical College of Wisconsin

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Responsible Party: Lubna Chaudhary, Assistant Professor, Medical College of Wisconsin Identifier: NCT03219476     History of Changes
Other Study ID Numbers: PRO30178
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Lubna Chaudhary, Medical College of Wisconsin:
aromatase inhibitor
breast cancer
estrogen receptor
progesterone receptor
endocrine-targeted therapy
Anti-estrogen therapy
Neoadjuvant Treatment
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents