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

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

Detailed Description
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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.

Official Title
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A Pilot Study Evaluating Megestrol Acetate Modulation in Advanced Breast Cancer With Positive Hormonal Receptor

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Drug: Megestrol Acetate 160Mg Tablet
* Drug: Anastrozole 1Mg Tablet
* Drug: Letrozole 2.5Mg Tablet
* Drug: Exemestane 25 MG
* Drug: Tamoxifen 20Mg Tablet
* Drug: Fulvestrant 50Mg Solution for Injection


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Megestrol acetate<br>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. | Drug: Megestrol Acetate 160Mg Tablet<br>* Megestrol acetate 160 mg PO daily<br>* Other names: MA;|
| Active Comparator: Anastrozole<br>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. | Drug: Anastrozole 1Mg Tablet<br>* Anastrozole 1 mg PO daily OR<br>* Other names: Anastrozole;|
| Active Comparator: Letrozole<br>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. | Drug: Letrozole 2.5Mg Tablet<br>* Letrozole 2.5 mg PO daily OR<br>* Other names: Letrozole;|
| Active Comparator: Exemestane<br>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. | Drug: Exemestane 25 MG<br>* Exemestane 25 mg PO daily<br>* Other names: Exemestane;|
| Active Comparator: Tamoxifen<br>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. | Drug: Tamoxifen 20Mg Tablet<br>* Tamoxifen 20 mg PO daily<br>* Other names: Tamoxifen;|
| Active Comparator: Fulvestrant<br>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. | Drug: Fulvestrant 50Mg Solution for Injection<br>* Fulvestrant 500 mg IM d1, d14, d28 and q28 days<br>* Other names: Fulvestrant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | 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 | From date of randomization until disease progression or death due to any cause, assessed up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From date of randomization until the date of death from any cause, assessed up to 18 months | From date of randomization until death, assessed up to 18 months | 
| Clinical benefit | 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 | Partial response and stable disease for more than 24 weeks, assessed up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Megestrol Acetate, Steroid, Receptors