Mifepristone for Breast Cancer Patients With Higher Levels of Progesterone Receptor Isoform A Than Isoform B.

NCT02651844 | Completed DMC

• 1 other identifier: PIDC-2012-0084
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

• Seventy per cent of breast cancers express estrogen (ER) and progesterone receptors (PR) and respond to endocrine treatment.
• Actual therapy targets ER.
• There is enough evidence that progestins participate regulating breast cancer growth.
• Antiprogestins block cell proliferation and increase apoptosis in breast cancer models which express high levels of PRA.
• Antiprogestins have been used to treat breast cancer patients that failed to other treatments; benefits were seen in selected patients.
• Mifepristone (MFP) is currently used for medical abortion and for the treatment of Cushing disease.
• MFP might exert agonistic effects when PRB isoform is activated by cAMP. This makes mandatory the evaluation of the PR isoform ratio in breast cancer patients in which MFP is a therapeutic possibility. Main Goal To evaluate if therapeutic doses of MFP exert beneficial effects on breast cancers expressing levels of PRA higher than those of PRB, evaluated as an inhibition in proliferation markers and/or an increase in apoptotic markers.
• Eligibility
• Postmenopausal women (one year after menses stop).
• Women with tumors showing ratios of PRA/PRB higher than 1.5 and PR higher than 50%.
• Women without previous treatment.
• All clinical stages with tumors larger than 1.5 cm.
• Patients without autoimmune diseases and/or asthma.
• Study design
• Open Interventional.
• Twenty women will take MFP (200 mg) p.o. once /day during 14 days. As for preliminary studies, to reach this number the investigators will have to evaluate 80-100 patients.
• Surgery is performed 14 days after treatment initiation, 24 hs after last dose.
• PR isoform ratio will be evaluated by western blots (WB) in one core biopsy. Additional cores will be used for diagnosis, immunohistochemistry (IHC) of PR, Ki-67 and other markers.
• At surgery samples will be frozen for molecular studies and fixed and processed for pathological evaluation.
• Wilcoxon signed rank test will be used to evaluate differences in biomarker expression between core biopsy and surgical samples of each patient.
• Blood will be collected before treatment initiation and prior to final surgery.
• Mammographic and echographic studies will be carried out before and after treatment.

Conditions

Breast Cancer

Keywords

Progesterone receptor isoforms; Antiprogestins; Mifepristone; Neoadjuvant; Breast cancer

Outcome Measures

Primary Outcomes (1)

• Measurable decrease in tumor cell proliferation from baseline to time of surgery

  Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery, evaluating if there is a decrease in the proliferating index (Ki-67 expression by immunohistochemistry). Positive response: differences higher than 30%.

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

Secondary Outcomes (2)

• Measurable increases in apoptotic markers from baseline to time of surgery

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

• Measurable changes in signaling pathways downstream PR

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

Other Outcomes (3)

• Changes in tumor size

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

• RNAseq analysis of gene expression and Proteomics to evaluate possible deregulated pathways

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

• Measure serum Mifepristone levels after 7/14 days Mifepristone treatment and other steroid hormone precursors

  Baseline to time of surgery (14 days of treatment between biopsy core and surgery), and an intermediate timepoint

Study Arms (1)

Mifepristone

EXPERIMENTAL

Tablets of Mifepristone 200 mg p.o. once a day during 14 days between biopsy and surgery after confirming inclusion criteria

Drug: Mifepristone

Interventions

Mifepristone DRUG

At the time a patient enters the protocol, 14 pills will be given to the personnel responsible of giving the patient the medicine at her home (This was a special requirement from the Argentine Authorities). Patients and personnel will sign the form each then she gets the medication and after that the signed form will be kept at the CRF file.

Also known as: RU-486

Mifepristone

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women (one year after menses stop)
• Confirmed diagnosis of breast cancer
• Tumors with higher expression PR \> 50 % measured by IHC and PRA/RPB ratio equal or higher than 1.5 measured by WB
• All clinical stages with tumor size greater than 1.5 cm to allow obtaining material from biopsy cores
• OMS condition: 1 Adequate function of organs and systems
• Hematopoietic parameters:
• Hemoglobin: 10 gr/mL
• Neutrophil counting: 1.500/mm3
• CD4 counting: 400/mm3
• Platelets counting: 100.000/mm3 Liver parameters
• Total albumin: 1.5 fold normal limit
• AST/ALT: 1.5 fold normal limit Renal
• Creatinine: 1.5 fold normal limit 6. Absence of other controlled disease 7. Patients willing to sign consent

You may not qualify if:

• Patients with no recommended surgery
• Patients which have received any other treatment for this cancer
• Patients expressing ER but expressing PRA/PRB levels lower than 1.5
• Hepatitis infection (HBV o HCV)
• HIV infection.
• Cognitive alterations which limit the understanding of the protocol or compliance to the protocol
• Prolonged QT/QTc basal interval

Sponsors & Collaborators

• Hospital Provincial Magdalena V. de Martínez: lead
• National Agency for Scientific and Technological Promotion, Argentina: collaborator
• Instituto de Biología y Medicina Experimental (IBYME-CONICET): collaborator

Study Sites (1)

HospitalPMVM

General Pacheco, Buenos Aires, 1617, Argentina

Location

Related Publications (23)

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Claudia Lanari, PhD

  IBYME-CONICET

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 11, 2016
• Study Start: April 1, 2016
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: May 6, 2022

Record last verified: 2020-07

Locations

AR (1)