Clinical trial NCT03219476: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2017-07-17
Enrollment: 37
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.
timeFrame: At four weeks.
Secondary outcomes:
measure: Number of Subjects Who Achieve Complete Radiographic Response.
timeFrame: At four weeks.
measure: Number of Subjects Who Achieve a Partial Radiographic Response.
timeFrame: At four weeks.
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Lubna Chaudhary
role: PRINCIPAL_INVESTIGATOR
References: