A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer (MEGA)

Instituto Nacional de Cancer, Brazil

Status and phase: Unknown; Phase 2

Conditions: Breast Neoplasm

Treatments: Drug: Megestrol Acetate 160Mg Tablet; Drug: Letrozole 2.5Mg Tablet; Drug: Tamoxifen 20Mg Tablet; Drug: Fulvestrant 50Mg Solution for Injection; Drug: Anastrozole 1Mg Tablet; Drug: Exemestane 25 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT03024580

64/16

Details and patient eligibility

About

This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors in advanced breast cancer.

Full description

Progesterone receptor (PR) expression has been considered a biomarker of oestrogen receptor-α (ERα) activity. This longstanding relationship has been recently challenged and instead of being merely an ERα-induced gene target, PR may be a critical determinant of ERα activity. The functional significance of this steroid receptor crosstalk is regulation of a gene expression program associated with low tumorigenicity; hence, better disease outcome. Genomic alterations in the PR genomic locus seem to be a relatively common mechanism for reduction of PR expression, which may consequently lead to altered ERα chromatin binding and target gene expression patterns that increase breast tumorigenicity and confers a poor clinical outcome. This ERα-PR crosstalk may be directly influenced by many variables, including the relative receptor levels and the hormonal milieu.

ER-positive advanced breast cancer is a heterogeneous group of diseases with considerable variability in outcome to a range of treatments. Prior response predicts the likelihood of subsequent benefit from another endocrine agent and this should be taken into account in the treatment decision process when assessing whether to prescribe a subsequent endocrine therapy. Despite the enormous progress made regarding the elucidation of breast cancer subgroups and their molecular drivers, most information comes from primary tumors. MA lacks cross-resistance and is active after acquired resistance to potent AI. This pilot trial evaluates in vivo MA modulation of steroidal receptors in advanced breast cancer.

Enrollment: 20 estimated patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion criteria

• Metastatic breast cancer with ER and/or PR positive (primary tumor)
• Metastatic site amenable to biopsy

Exclusion criteria

• Platelet count below 100,000 / mm3
• Renal or hepatic impairment
• Coagulation disorder

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 6 patient groups

Megestrol acetate

Experimental group

Description:

Megestrol acetate 160 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Megestrol Acetate 160Mg Tablet

Anastrozole

Active Comparator group

Description:

Anastrozole 1 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Anastrozole 1Mg Tablet

Letrozole

Active Comparator group

Description:

Letrozole 2.5 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Letrozole 2.5Mg Tablet

Exemestane

Active Comparator group

Description:

Exemestane 25 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Exemestane 25 MG

Tamoxifen

Active Comparator group

Description:

Tamoxifen 20 mg PO daily until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Tamoxifen 20Mg Tablet

Fulvestrant

Active Comparator group

Description:

Fulvestrant 500 mg intramuscularly (IM) d1, d14, d28 and q28 days until disease progression or unacceptable toxicity Tumor biopsy and blood collection before treatment initiation and at the time of disease progression.

Treatment:

Drug: Fulvestrant 50Mg Solution for Injection