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A Window of Opportunity Study of Pre-operative Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Breast Hormone Receptor Positive (HR+) Human Epidermal Receptor 2 Negative (HER2-) Breast Cancer.

NCT03906669

Description:

A phase II randomised, open label study of pre-operative endocrine therapy with & without prometrium in postmenopausal women with early stage breast hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Window of Opportunity Study of Pre-operative Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Breast Hormone Receptor Positive (HR+) Human Epidermal Receptor 2 Negative (HER2-) Breast Cancer.
  • Official Title: A Window of Opportunity Study of Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Hormone Receptor-positive Breast Cancer.

Clinical Trial IDs

  • ORG STUDY ID: ACTRN1261000928213
  • NCT ID: NCT03906669

Conditions

  • Early-stage Breast Cancer
  • Hormone Receptor Positive Tumor

Interventions

DrugSynonymsArms
LetrozoleLetrozole
Letrozole and PrometriumLetrozole and Prometrium
Tamoxifen and PrometriumTamoxifen and Prometrium

Purpose

A phase II randomised, open label study of pre-operative endocrine therapy with & without prometrium in postmenopausal women with early stage breast hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) breast cancer.

Detailed Description

      There is bidirectional interplay between the progesterone receptor (PR) and oestrogen
      receptor (ER) in human breast cancers. There is evidence for a reprogramming of ER chromatin
      binding sites with 470 genes differentially regulated by dual treatment with estrogen plus
      progestogen compared to estrogen alone in breast cancer cell lines. Functionally, there was
      an additive anti-cancer effect with the addition of natural progesterone to endocrine therapy
      in preclinical breast cancer models.

      This is a phase II multi-site, randomised, open-label, three-arm, study in 200 postmenopausal
      women with early-stage ER+, PR+, HER2-negative breast cancer. Eligible patients will be
      randomised (1:1:1) to receive 14 days of intervention with either letrozole 2.5mg PO daily
      (arm 1), letrozole 2.5mg + prometrium 300mg PO daily (arm 2) or tamoxifen 20mg + prometrium
      300mg PO daily (arm 3), between diagnosis of breast cancer and definitive surgery.
    

Trial Arms

NameTypeDescriptionInterventions
LetrozoleActive ComparatorLetrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
  • Letrozole
Letrozole and PrometriumExperimentalLetrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
  • Letrozole and Prometrium
Tamoxifen and PrometriumExperimentalTamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
  • Tamoxifen and Prometrium

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed ER+ and PR+ breast cancer (defined as ≥10% positive staining
             cells)

          2. Histologically confirmed HER2-negative breast cancer (defined as IHC 0-1 and/or
             FISH/CISH <2.2)

          3. Tumour size ≥1 cm as measured by ultrasound and/or mammogram

          4. Ability to understand all patient information and informed-consent documents, written
             informed consent to participate in the trial, and to avail tissue and blood samples
             for research

          5. Aged 18 years or older

        Exclusion Criteria:

          1. Women currently on hormone therapies, including hormone replacement therapy and oral
             contraceptive pill

          2. Locally advanced/inoperable and inflammatory breast cancer

          3. Planned for a mastectomy (due to increased risk of venous thromboembolism)

          4. Clinical evidence of metastatic disease

          5. Patients treated with other preoperative systemic therapies

          6. Nut allergy (prometrium contains peanut oil)

          7. Prior history of uterine cancer, deep vein thrombosis, pulmonary embolism or clotting
             disorder

          8. Women who are pregnant or breast-feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Geometric mean suppression of proliferation marker Ki67
Time Frame:After two weeks of intervention, compared with baseline
Safety Issue:
Description:The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline

Secondary Outcome Measures

Measure:Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:2 years
Safety Issue:
Description:Safety and tolerability of combination therapy (NCI-CTCAE v4.0)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:St. Vincent's Hospital-Manhattan

Trial Keywords

  • early stage breast cancer
  • prometrium
  • progesterone
  • post-menopausal
  • endocrine therapy

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