Clinical trial NCT03024580: A Study Evaluating Megestrol Acetate Modulation in Hormone Receptor Positive Advanced Breast Cancer
Official title: A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Neoplasm
Keywords: Megestrol Acetate
Steroid, Receptors
Lead sponsor: Instituto Nacional de Cancer, Brazil
Sponsor class: OTHER_GOV
Collaborators: name: Cancer Research UK Cambridge Institute
First posted: 2017-01-19
Enrollment: 20
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: From date of randomization until disease progression or death due to any cause, assessed up to 18 months
Secondary outcomes:
measure: Overall survival
timeFrame: From date of randomization until death, assessed up to 18 months
measure: Clinical benefit
timeFrame: Partial response and stable disease for more than 24 weeks, assessed up to 18 months
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Hospital do Cancer III
Study officials:
affiliation: Instituto Nacional de Cancer, Brazil
name: José Bines, MD, PhD
role: STUDY_CHAIR
affiliation: Cancer Research UK Cambridge Institute
name: Jason Carroll, PhD
role: STUDY_CHAIR
References: