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Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Node-Negative Breast Cancer

Primary Purpose

Breast Cancer, Invasive Breast Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Anastrozole
Letrozole
Exemestane
Tamoxifen
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring aromatase inhibitor, breast cancer, estrogen receptor, progesterone receptor, endocrine-targeted therapy, Anti-estrogen therapy, HR+, HER2-negative, Neoadjuvant Treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
  • HER2/neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
  • Eastern Cooperative Oncology Group (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:

  • American Joint Committee on Cancer (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.

Sites / Locations

  • Froedtert Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant endocrine therapy treatment (physician's choice)

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.
ImmunoHistoChemistry (IHC) will be used. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+ (up to 25% of cells stained), it's called "HER2 negative." If the score is 2+ (approximately 50% of cells stained), it's called "borderline." A score of 3+ (approximately 75% or more of cells stained) is called "HER2 positive." Upregulation means increased staining from a prior observation; Downregulation means decreased staining from a prior observation; and No Change means similar staining from a prior observation.

Secondary Outcome Measures

Number of Subjects Who Achieve Complete Radiographic Response.
This will be assessed by World Health Organization (WHO) criteria: Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated. Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).
Number of Subjects Who Achieve a Partial Radiographic Response.
This will be assessed by World Health Organization (WHO) criteria: Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated. Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).

Full Information

First Posted
July 12, 2017
Last Updated
July 24, 2023
Sponsor
Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT03219476
Brief Title
Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Node-Negative Breast Cancer
Official Title
Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 5, 2017 (Actual)
Primary Completion Date
February 4, 2020 (Actual)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.
Detailed Description
STUDY RATIONALE: Patients with hormone receptor (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 human epidermal growth factor receptor (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Invasive Breast Cancer
Keywords
aromatase inhibitor, breast cancer, estrogen receptor, progesterone receptor, endocrine-targeted therapy, Anti-estrogen therapy, HR+, HER2-negative, Neoadjuvant Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant endocrine therapy treatment (physician's choice)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Arimidex
Intervention Description
1 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Femara
Intervention Description
2.5mg once daily.
Intervention Type
Drug
Intervention Name(s)
Exemestane
Other Intervention Name(s)
Aromasin
Intervention Description
25 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Other Intervention Name(s)
Soltamox
Intervention Description
20 mg once daily.
Primary Outcome Measure Information:
Title
Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.
Description
ImmunoHistoChemistry (IHC) will be used. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+ (up to 25% of cells stained), it's called "HER2 negative." If the score is 2+ (approximately 50% of cells stained), it's called "borderline." A score of 3+ (approximately 75% or more of cells stained) is called "HER2 positive." Upregulation means increased staining from a prior observation; Downregulation means decreased staining from a prior observation; and No Change means similar staining from a prior observation.
Time Frame
At four weeks.
Secondary Outcome Measure Information:
Title
Number of Subjects Who Achieve Complete Radiographic Response.
Description
This will be assessed by World Health Organization (WHO) criteria: Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated. Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).
Time Frame
At four weeks.
Title
Number of Subjects Who Achieve a Partial Radiographic Response.
Description
This will be assessed by World Health Organization (WHO) criteria: Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy. No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated. Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).
Time Frame
At four weeks.

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Cis females.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. HER2/neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Eastern Cooperative Oncology Group (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: American Joint Committee on Cancer (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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lubna Chaudhary
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Node-Negative Breast Cancer

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