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 | Unknown Phase 2

• 1 other identifier: ACTRN1261000928213
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Early-stage Breast Cancer; Hormone Receptor Positive Tumor

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Geometric mean suppression of proliferation marker Ki67

  The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline

  After two weeks of intervention, compared with baseline

Secondary Outcomes (1)

• Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

Other Outcomes (3)

• Define a gene set as a predictive biomarker for a reduction in Ki67

  4 years

• Evaluate changes in the apoptotic markers Bcl-2 and Caspase 3 in the tumors following intervention

  4 years

• Evaluate changes in ER, PR, AR, FoxA1, Cyclin D1 protein and mRNA expression in the tumors following intervention

  4 years

Study Arms (3)

Letrozole

ACTIVE COMPARATOR

Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Drug: Letrozole

Letrozole and Prometrium

EXPERIMENTAL

Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Drug: Letrozole and Prometrium

Tamoxifen and Prometrium

EXPERIMENTAL

Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Drug: Tamoxifen and Prometrium

Interventions

Letrozole DRUG

PO daily for 14 days

Letrozole

Letrozole and Prometrium DRUG

PO daily for 14 days

Letrozole and Prometrium

Tamoxifen and Prometrium DRUG

PO daily for 14 days

Tamoxifen and Prometrium

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed ER+ and PR+ breast cancer (defined as ≥10% positive staining cells)
• Histologically confirmed HER2-negative breast cancer (defined as IHC 0-1 and/or FISH/CISH \<2.2)
• Tumour size ≥1 cm as measured by ultrasound and/or mammogram
• 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
• Aged 18 years or older

You may not qualify if:

• Women currently on hormone therapies, including hormone replacement therapy and oral contraceptive pill
• Locally advanced/inoperable and inflammatory breast cancer
• Planned for a mastectomy (due to increased risk of venous thromboembolism)
• Clinical evidence of metastatic disease
• Patients treated with other preoperative systemic therapies
• Nut allergy (prometrium contains peanut oil)
• Prior history of uterine cancer, deep vein thrombosis, pulmonary embolism or clotting disorder
• Women who are pregnant or breast-feeding

Sponsors & Collaborators

• St Vincent's Hospital: lead

Study Sites (1)

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

RECRUITING

Related Publications (2)

• Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERalpha action in breast cancer. Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8.

  PMID: 26153859 BACKGROUND

• Lim E, Tarulli G, Portman N, Hickey TE, Tilley WD, Palmieri C. Pushing estrogen receptor around in breast cancer. Endocr Relat Cancer. 2016 Dec;23(12):T227-T241. doi: 10.1530/ERC-16-0427. Epub 2016 Oct 11.

  PMID: 27729416 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Progesterone; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Elgene Lim, MBBS FRACP PhD

  Garvan Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Kent

CONTACT

+61293555611; SVHS.CancerResearch@svha.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: April 8, 2019
• Study Start: March 20, 2018
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)