Description:
This is an exploratory interventional study that initiates standard-of-care anti-estrogen
treatment preoperatively for four weeks.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
PRO30178
- NCT ID:
NCT03219476
Conditions
- Breast Cancer
- Invasive Breast Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Anastrozole | Arimidex | Neoadjuvant endocrine therapy treatment (physician's choice) |
| Letrozole | Femara | Neoadjuvant endocrine therapy treatment (physician's choice) |
| Exemestane | Aromasin | Neoadjuvant endocrine therapy treatment (physician's choice) |
| Tamoxifen | Soltamox | Neoadjuvant endocrine therapy treatment (physician's choice) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Neoadjuvant endocrine therapy treatment (physician's choice) | Experimental | 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. | - Anastrozole
- Letrozole
- Exemestane
- Tamoxifen
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | The proportion of upregulated HER proteins after treatment. |
| Time Frame: | At four weeks. |
| Safety Issue: | |
| Description: | An exact binomial one sample test of proportions will be used. |
Secondary Outcome Measures
| Measure: | The differences in proportion of upregulated HER proteins between the high difference in Ki-67 and low difference in Ki-67 groups. |
| Time Frame: | At four weeks. |
| Safety Issue: | |
| Description: | Two sample tests of proportions will be used. |
| Measure: | Numbers of subjects who achieve complete radiographic response. |
| Time Frame: | At four weeks. |
| Safety Issue: | |
| Description: | This will be assessed by World Health Organization (WHO) criteria. |
| Measure: | Numbers of subjects who achieve a partial radiographic response. |
| Time Frame: | At four weeks. |
| Safety Issue: | |
| Description: | This will be assessed by World Health Organization (WHO) criteria. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Medical College of Wisconsin |
Trial Keywords
- aromatase inhibitor
- breast cancer
- estrogen receptor
- progesterone receptor
- endocrine-targeted therapy
- Anti-estrogen therapy
- HR+
- HER2-negative
- Neoadjuvant Treatment
Last Updated
July 20, 2020
