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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

NCT03219476

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

DrugSynonymsArms
AnastrozoleNeoadjuvant endocrine therapy treatment (physician's choice)
LetrozoleNeoadjuvant endocrine therapy treatment (physician's choice)
ExemestaneNeoadjuvant endocrine therapy treatment (physician's choice)
TamoxifenNeoadjuvant 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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Neoadjuvant endocrine therapy treatment (physician's choice)ExperimentalOnce 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Protein expression will be quantified on slides, using optimized immunohistochemical protocols for planned study biomarkers.
Time Frame:At four weeks.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Patient outcomes (e.g., distant recurrences) will be assessed by chart review in follow-up.
Time Frame:Five years.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status: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

February 8, 2018