Breast Neoplasm
Conditions
Keywords
Megestrol Acetate, Steroid, Receptors
Brief summary
This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors in advanced breast cancer.
Detailed 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.
Interventions
DRUGMegestrol Acetate 160Mg Tablet
Megestrol acetate 160 mg PO daily
DRUGAnastrozole 1Mg Tablet
Anastrozole 1 mg PO daily OR
Letrozole 2.5 mg PO daily OR
DRUGExemestane 25 MG
Exemestane 25 mg PO daily
DRUGTamoxifen 20Mg Tablet
Tamoxifen 20 mg PO daily
DRUGFulvestrant 50Mg Solution for Injection
Fulvestrant 500 mg IM d1, d14, d28 and q28 days
Sponsors
Cancer Research UK Cambridge Institute
Instituto Nacional de Cancer, Brazil
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | From date of randomization until disease progression or death due to any cause, assessed up to 18 months | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From date of randomization until death, assessed up to 18 months | From date of randomization until the date of death from any cause, assessed up to 18 months |
| Clinical benefit | Partial response and stable disease for more than 24 weeks, assessed up to 18 months | Partial response and stable disease for more than 24 weeks, as per RECIST criteria, from date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 18 months |
Countries
Brazil
Contacts
Primary ContactRenata Obadia, RN
Outcome results
None listed