Clinical Trials /

Anastrozole and Letrozole After Surgery for the Treatment of Stage I-III Breast Cancer

NCT04294225

Description:

This phase II trial studies how well anastrozole and letrozole after surgery work in treating patients with stage I-III breast cancer. Drugs, such as anastrozole and letrozole may stop the growth of tumor cells by decreasing the amount of estrogen made by the body. Giving anastrozole and letrozole after surgery may prevent breast cancer from coming back (recurrence).

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anastrozole and Letrozole After Surgery for the Treatment of Stage I-III Breast Cancer
  • Official Title: Pharmacodynamic Study of Estrogen Suppression Threshold-Directed Therapy (ESTDT) of Anastrozole as Adjuvant Therapy for Early Stage Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: MC1931
  • SECONDARY ID: NCI-2020-01062
  • SECONDARY ID: MC1931
  • SECONDARY ID: P30CA015083
  • SECONDARY ID: P50CA116201
  • NCT ID: NCT04294225

Conditions

  • Anatomic Stage I Breast Cancer AJCC v8
  • Anatomic Stage IA Breast Cancer AJCC v8
  • Anatomic Stage IB Breast Cancer AJCC v8
  • Anatomic Stage II Breast Cancer AJCC v8
  • Anatomic Stage IIA Breast Cancer AJCC v8
  • Anatomic Stage IIB Breast Cancer AJCC v8
  • Anatomic Stage III Breast Cancer AJCC v8
  • Anatomic Stage IIIA Breast Cancer AJCC v8
  • Anatomic Stage IIIB Breast Cancer AJCC v8
  • Anatomic Stage IIIC Breast Cancer AJCC v8
  • Early-Stage Breast Carcinoma
  • Invasive Breast Carcinoma
  • Prognostic Stage I Breast Cancer AJCC v8
  • Prognostic Stage IA Breast Cancer AJCC v8
  • Prognostic Stage IB Breast Cancer AJCC v8
  • Prognostic Stage II Breast Cancer AJCC v8
  • Prognostic Stage IIA Breast Cancer AJCC v8
  • Prognostic Stage IIB Breast Cancer AJCC v8
  • Prognostic Stage III Breast Cancer AJCC v8
  • Prognostic Stage IIIA Breast Cancer AJCC v8
  • Prognostic Stage IIIB Breast Cancer AJCC v8
  • Prognostic Stage IIIC Breast Cancer AJCC v8

Interventions

DrugSynonymsArms
AnastrozoleAnastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033Treatment (anastrozole, letrozole)
LetrozoleCGS 20267, FemaraTreatment (anastrozole, letrozole)

Purpose

This phase II trial studies how well anastrozole and letrozole after surgery work in treating patients with stage I-III breast cancer. Drugs, such as anastrozole and letrozole may stop the growth of tumor cells by decreasing the amount of estrogen made by the body. Giving anastrozole and letrozole after surgery may prevent breast cancer from coming back (recurrence).

Detailed Description

      PRIMARY OBJECTIVE:

      I. To estimate the proportion of women who have adequate estrone (E1) and estradiol (E2)
      suppression after 8-10 weeks of adjuvant anastrozole 10 mg once daily (ANA10) having had
      inadequate E1 and E2 suppression after 8-10 weeks of standard dose anastrozole 1 mg once
      daily (ANA1).

      SECONDARY OBJECTIVES:

      I. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of
      adjuvant ANA1.

      II. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of
      adjuvant ANA1 whose E1 and E2 levels remain elevated after 8-10 weeks of adjuvant ANA10.

      III. To examine the toxicity profile of ANA1 over the 8-10 weeks of treatment, ANA10 over the
      8-10 weeks of treatment, and letrozole over the 8-10 weeks of treatment.

      IV. To examine concentrations of anastrozole at both the ANA1 and ANA10 dose levels.

      V. To examine E1 and E2 concentrations, as well as letrozole drug levels, in patients
      receiving letrozole (following ANA10).

      VI. To bank deoxyribonucleic acid (DNA) for examination of single-nucleotide polymorphism
      (SNP)-set(s) determined in the ongoing Mayo Clinic Breast Cancer Specialized Program of
      Research Excellence (SPORE) Project 4.

      EXPLORATORY OBJECTIVE:

      I. To examine association between clinical variables such as age, age at menopause, BMI,
      receipt of chemotherapy, chemotherapy regimen and dose on E1 and E2 levels after 8-10 weeks
      of ANA10.

      OUTLINE:

      Patients receive anastrozole orally (PO) once daily (QD) for 56-70 days (8-10 weeks).
      Patients with E1 >= 1.3 pg/ml and E2 >= 0.5 pg/ml continue to receive anastrozole PO QD for
      another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks.
      Treatment continues in the absence of disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (anastrozole, letrozole)ExperimentalPatients receive anastrozole PO QD for 56-70 days (8-10 weeks). Patients with E1 >= 1.3 pg/ml and E2 >= 0.5 pg/ml continue to receive anastrozole PO QD for another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • Anastrozole
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  REGISTRATION-INCLUSION CRITERIA

          -  Disease characteristics:

               -  Histological confirmation of invasive breast carcinoma.

               -  Stage I-III breast cancer

               -  Estrogen receptor (ER) positive disease according to American Society of Clinical
                  Oncology (ASCO)/College of American Pathologists (CAP) guidelines as ER >= 1%
                  positive nuclear staining

          -  Completion of all planned cancer treatments =< 60 days prior to registration:

               -  Surgical resection of breast and nodal surgery; (NOTE: Reconstructive surgery
                  does not have to be completed)

               -  Adjuvant radiation therapy, if needed; and

               -  Neoadjuvant and/or adjuvant chemotherapy, if needed

          -  Post-menopausal defined as

               -  Age >= 60 and amenorrhea > 12 consecutive months OR

               -  Previous bilateral oophorectomy OR

               -  Age < 60 and amenorrhea > 12 consecutive months and documented follicle
                  stimulating hormone (FSH) level within post-menopausal range according to
                  institutional standard

                    -  NOTE: Patients who did not meet these criteria at time of diagnosis and
                       received pre-operative (neoadjuvant) or post-operative (adjuvant)
                       chemotherapy will not be allowed to participate

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to
             registration)

          -  Platelet count >= 70,000/mm^3 (obtained =< 14 days prior to registration)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to
             registration)

          -  Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained
             =< 14 days prior to registration)

          -  Ability to swallow oral medication

          -  Provide written informed consent

          -  Willingness to provide mandatory blood specimens for correlative research

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study)

          -  RE-REGISTRATION-INCLUSION CRITERIA

          -  Confirmation that baseline blood sample was drawn and submitted

          -  Blood estrogen levels after cycle 1 anastrozole (ANA1) must meet the following
             criteria:

               -  E1 >= 1.3 pg/ml, AND

               -  E2 >= 0.5 pg/ml

        Exclusion Criteria:

          -  REGISTRATION-EXCLUSION CRITERIA

          -  Pre-menopausal women receiving ovarian function suppression (goserelin, leuprolide,
             etc.)

          -  Stage IV (metastatic) breast cancer

          -  HER2 positive breast cancer as defined by

               -  HER2 immunohistochemistry (IHC) >= 3+

               -  HER2/CEP17 >= 2.0

               -  HER2/CEP17 < 2.0 and average HER2 copy number of >= 6.0 signals/cell

          -  Prior endocrine therapy for this breast cancer

          -  Currently receiving any of the following cancer-directed therapies:

               -  Radiation therapy

               -  Systemic therapy such as chemotherapy (standard or investigational)

          -  Bisphosphonate therapy started < 4 weeks prior to registration.

               -  NOTE: If patient is currently on bisphosphonate therapy she must be on stable
                  dose for >= 4 weeks prior to registration. Patients not currently taking
                  bisphosphonates will be allowed to start bisphosphonate therapy after completion
                  of anastrozole (1mg and 10 mg daily [if given]). Information regarding
                  bisphosphonate therapy will be collected

          -  Current use of systemic or topical exogenous estrogen or progesterone (menopausal
             hormone replacement therapy [HRT])

          -  Prior ovarian function suppression (leuprolide, goserelin, etc) or prior prevention
             therapy with an aromatase inhibitor.

               -  NOTE: Prior prevention therapy with a selective estrogen receptor modulator
                  (SERM) (tamoxifen, raloxifene, etc.) is allowed

          -  Inability to provide informed consent

          -  History of contralateral ductal carcinoma in situ (DCIS) or invasive breast cancer

          -  Concurrent active malignancy or history of malignancy =< 3 years prior to
             registration.

               -  NOTE: Exceptions allowed for successfully treated cervical carcinoma in situ,
                  lobular carcinoma in situ of the breast, papillary thyroid cancer, or
                  non-melanoma skin cancer
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 10 weeks
Safety Issue:
Description:Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Secondary Outcome Measures

Measure:The percent change in E1 and E2 concentrations
Time Frame:8-10 weeks after treatment of anastrozole 10mg and letrozole 2.5 mg
Safety Issue:
Description:Descriptive statistics will be used. The percent change in E1 and E2 concentrations from pre-AI levels will be determined and graphically depicted using spider plots.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mayo Clinic

Last Updated

March 2, 2020