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

NCT ID: NCT03024580

Last Updated: 2019-08-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-06
• Study Completion Date: 2020-09-30

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.

Conditions

Breast Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Megestrol acetate

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.

Group Type: EXPERIMENTAL

Megestrol Acetate 160Mg Tablet

Intervention Type: DRUG

Megestrol acetate 160 mg PO daily

Anastrozole

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.

Group Type: ACTIVE_COMPARATOR

Anastrozole 1Mg Tablet

Intervention Type: DRUG

Anastrozole 1 mg PO daily OR

Letrozole

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.

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5Mg Tablet

Intervention Type: DRUG

Letrozole 2.5 mg PO daily OR

Exemestane

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.

Group Type: ACTIVE_COMPARATOR

Exemestane 25 MG

Intervention Type: DRUG

Exemestane 25 mg PO daily

Tamoxifen

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.

Group Type: ACTIVE_COMPARATOR

Tamoxifen 20Mg Tablet

Intervention Type: DRUG

Tamoxifen 20 mg PO daily

Fulvestrant

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.

Group Type: ACTIVE_COMPARATOR

Fulvestrant 50Mg Solution for Injection

Intervention Type: DRUG

Fulvestrant 500 mg IM d1, d14, d28 and q28 days

Interventions

Megestrol Acetate 160Mg Tablet

Megestrol acetate 160 mg PO daily

Intervention Type: DRUG

Anastrozole 1Mg Tablet

Anastrozole 1 mg PO daily OR

Intervention Type: DRUG

Letrozole 2.5Mg Tablet

Letrozole 2.5 mg PO daily OR

Intervention Type: DRUG

Exemestane 25 MG

Exemestane 25 mg PO daily

Intervention Type: DRUG

Tamoxifen 20Mg Tablet

Tamoxifen 20 mg PO daily

Intervention Type: DRUG

Fulvestrant 50Mg Solution for Injection

Fulvestrant 500 mg IM d1, d14, d28 and q28 days

Intervention Type: DRUG

Other Intervention Names

MA; Anastrozole; Letrozole; Exemestane; Tamoxifen; Fulvestrant

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

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK Cambridge Institute

OTHER

Sponsor Role: collaborator

Instituto Nacional de Cancer, Brazil

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José Bines, MD, PhD

Role: STUDY_CHAIR

Instituto Nacional de Cancer, Brazil

Jason Carroll, PhD

Role: STUDY_CHAIR

Cancer Research UK Cambridge Institute

Locations

Hospital do Cancer III

Rio de Janeiro, , Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Renata Obadia, RN

Role: CONTACT

robadia@inca.gov.br

552132073810

Facility Contacts

Renata Obadia, RN

Role: primary

robadia@inca.gov.br

552132073810

Other Identifiers

64/16

Identifier Type: -

Identifier Source: org_study_id