Clinical Trials /

Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer

NCT03747042

Description:

A short pre-surgical non-therapeutic trial involving postmenopausal women with newly diagnosed eR+, HeR2-negative operable breast cancers. After undergoing a core needle biopsy for tissue acquisition, study participants will take a 7- to 56-day (1-8 weeks) course of letrozole in accordance with standard of care. They will then undergo definitive surgical resection of their primary tumor (mastectomy vs lumpectomy) as per standard of care guidelines.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer
  • Official Title: Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: SCCC-11118; STU-2018-0015
  • NCT ID: NCT03747042

Conditions

  • Breast Cancer Female

Interventions

DrugSynonymsArms
LetrozoleTreatment

Purpose

A short pre-surgical non-therapeutic trial involving postmenopausal women with newly diagnosed eR+, HeR2-negative operable breast cancers. After undergoing a core needle biopsy for tissue acquisition, study participants will take a 7- to 56-day (1-8 weeks) course of letrozole in accordance with standard of care. They will then undergo definitive surgical resection of their primary tumor (mastectomy vs lumpectomy) as per standard of care guidelines.

Detailed Description

      Patients will receive a prescription for letrozole to be taken orally at a dose of 2.5 mg/day
      for 7-56 days to allow for variations in surgical scheduling. Patients are to undergo
      surgical resection of their tumor the day after the last dose of letrozole.

      Post-treatment tumor biopsies (a goal of 4-6 cores) will be obtained following 7-56 days of
      letrozole treatment on the day of surgery. Frozen AND formalin fixed core biopsies will be
      obtained whenever possible. The tissue will be used for study-specific assays as well as
      routine histopathology. Post-treatment core needle biopsy tissue will be obtained, whenever
      possible, by the surgeon intraoperatively at the time of routine surgical resection. A
      formalin-fixed paraffin embedded tumor block from the patient's surgical resection is also
      requested. This block will be used for a subset of the correlative studies if no tumor is
      obtained by the post treatment core biopsies. This block will be returned to pathology
      promptly after the correlative studies are completed.

      Surgical treatment (total mastectomy or segmental resection with lymph node evaluation if
      clinically indicated) will occur the day after completion of therapy.

      The primary lesion obtained at the time of the definitive surgical procedure (partial or
      total mastectomy) will be sent for standard of care histopathologic analysis; wherever
      possible intra-opearative cores from the central portion of the tumor will be obtained for
      study-specific assays. All specimens will be handled according to established institutional
      guidelines to maintain the accuracy of the analysis of tumor size and margin status.

      Following standard of care histopathologic analysis, additional paraffin-embedded sections
      will be submitted at a later time to the Simmons Cancer Tissue Core to determine tumor
      proliferation with Ki67 (MIB1Ab, Dako Cytomation) IHC. These tests are of no clinical utility
      and will be done for research purposes only.

      Frozen cores and/or peels from the formalin-fixed paraffin-embedded (FFPE) tumor blocks from
      the surgical specimen will be selected and/or macrodissected - when needed - based on ≥20%
      tumor cellularity as assessed by Dr. Sahoo, expert breast pathologist in the trial. These
      will be sent to Dr. Carlos Arteaga's laboratory for further testing.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalDrug: letrozole Take by mouth at a dose of 2.5 mg on days 7-56 Other: Blood Collection Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction Procedure: biopsy/lumpectomy/mastectomy Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          1. Eligibility waivers are not permitted. Subjects must meet all of the inclusion and
             exclusion criteria to be registered to the study. Study treatment may not begin until
             a subject is registered.

          2. Patients must provide informed written consent

          3. ECOG performance status 0-1.

          4. Clinical stage operable I, II or III invasive mammary carcinoma, which is ER-positive
             by IHC and HER2-negative by Herceptest (0 or 1+) or not amplified by FISH as per
             routine clinical testing Patients who have measurable residual tumor at the primary
             site Patients who will undergo surgical treatment with either segmental resection or
             total mastectomy

          5. Measurable tumor i. Measurable disease: a mass that can be reproducibly measured by
             physical exam and calipers or ultrasound and is at least 1 cm in size

          6. The pathology report from the initial diagnosis has been reviewed by either UTSW or
             Parkland Hospital, Department of Pathology and meets eligibility criteria. Available
             core biopsies from the time of diagnosis have been requested. These may include the
             paraffin block or sections from the paraffin-embedded tumor blocks.

          7. Post-menopausal female subjects ≥18 years of age, as defined by any of the following:

               -  Subjects at least 55 years of age;

               -  Subjects under 55 years of age and amenorrhoeic for at least 12 months or
                  follicle-stimulating hormone (FSH) values ≥40 IU/L and estradiol levels ≤20 IU/L;

               -  Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at
                  least 6 months.

               -  (There is no upper age limit for enrollment to this study)

          8. No prior chemotherapy for this primary breast cancer.

          9. Patients with a prior history of contralateral breast cancer are eligible if they have
             no evidence of recurrence of their initial primary breast cancer.

         10. Women may have been taking tamoxifen or raloxifene as a preventive agent prior to
             study entry but must have discontinued the drug for at least 21 days prior to study
             enrollment.

         11. Subjects must have ended hormone replacement therapy (HRT) (e.g., conjugated estrogens
             tablets, USP, [Premarin]), at least 7 days prior to receiving the first dose of
             randomized therapy.

         12. Patients must have adequate hepatic and renal function. All tests must be obtained
             less than 4 weeks from study entry. This includes:

               1. Creatinine <1.5X upper limits of normal

               2. Bilirubin, SGOT, SGPT <1.5X upper limits of normal

         13. Able to swallow and retain oral medication

        Exclusion Criteria:

          1. Patients with locally advanced disease who are candidates for other preoperative
             chemotherapy at the time of initial evaluation. This may include patients with locally
             advanced disease such as:

               -  Inflammatory breast cancer (T4d)

               -  Fixed axillary lymph node metastases (N2)

               -  Metastasis to ipsilateral internal mammary node (N3)

          2. Locally recurrent breast cancer

          3. Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)

          4. Serious medical illness that in the judgment of the treating physician places the
             patient at high risk of operative mortality.

          5. Severe uncontrolled malabsorption condition or disease (i.e. grade II/III diarrhea,
             severe malnutrition, short gut syndrome)

          6. Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.

          7. Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of letrozole.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measure Ki67 index in highly hormone-dependent breast cancers vs. those that are not
Time Frame:Within 8 to 57 days
Safety Issue:
Description:Ki67 index measured 1-8 weeks after therapy with letrozole to segregate hormone receptor-positive breast cancers that are highly hormone-dependent vs. those that are not

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Trial Keywords

  • ER-positive
  • HER2-negative
  • invasive mammary carcinoma

Last Updated