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| Name | Class |
|---|---|
| Cancer Research UK Cambridge Institute | OTHER |
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This pilot trial evaluates in vivo megestrol acetate (MA) modulation of steroidal receptors in advanced breast cancer.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Megestrol acetate | Experimental | 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. |
|
| Anastrozole | Active Comparator | 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. |
|
| Letrozole | Active Comparator | 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. |
|
| Exemestane | Active Comparator | 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. |
|
| Tamoxifen | Active Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Megestrol Acetate 160Mg Tablet | Drug | Megestrol acetate 160 mg PO daily |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Renata Obadia, RN | Contact | 552132073810 | robadia@inca.gov.br |
| Name | Affiliation | Role |
|---|---|---|
| José Bines, MD, PhD | Instituto Nacional de Cancer, Brazil | Study Chair |
| Jason Carroll, PhD | Cancer Research UK Cambridge Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital do Cancer III | Recruiting | Rio de Janeiro | 20560120 | Brazil |
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| Fulvestrant | Active Comparator | 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. |
|
| Anastrozole 1Mg Tablet | Drug | Anastrozole 1 mg PO daily OR |
|
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| Letrozole 2.5Mg Tablet | Drug | Letrozole 2.5 mg PO daily OR |
|
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| Exemestane 25 MG | Drug | Exemestane 25 mg PO daily |
|
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| Tamoxifen 20Mg Tablet | Drug | Tamoxifen 20 mg PO daily |
|
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| Fulvestrant 50Mg Solution for Injection | Drug | Fulvestrant 500 mg IM d1, d14, d28 and q28 days |
|
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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 |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D019290 | Megestrol Acetate |
| D013607 | Tablets |
| D000077384 | Anastrozole |
| D000077289 | Letrozole |
| C056516 | exemestane |
| D013629 | Tamoxifen |
| D000077267 | Fulvestrant |
| D012996 | Solutions |
| D007267 | Injections |
| ID | Term |
|---|---|
| D008535 | Megestrol |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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