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Trial record 37 of 52 for:    cushing's | Recruiting, Not yet recruiting, Available Studies

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

This study is currently recruiting participants.
Verified January 2016 by Hospital Provincial Magdalena V. de Martínez
Sponsor:
ClinicalTrials.gov Identifier:
NCT02651844
First Posted: January 11, 2016
Last Update Posted: June 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Agencia Nacional de Promoción de Ciencia y Tecnología, MINCYT
Instituto de Biología y Medicina Experimental (IBYME-CONICET)
Information provided by (Responsible Party):
Hospital Provincial Magdalena V. de Martínez
  Purpose
  • 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.

Condition Intervention
Breast Cancer Drug: Mifepristone

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mifepristone Treatment for Breast Cancer Patients Expressing Levels of Progesterone Receptor Isoform A (PRA) Higher Than Those of Isoform B (PRB): Neoadjuvant Therapy.

Resource links provided by NLM:


Further study details as provided by Hospital Provincial Magdalena V. de Martínez:

Primary Outcome Measures:
  • Measurable decrease in tumor cell proliferation from baseline to time of surgery [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and 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%.


Secondary Outcome Measures:
  • Measurable increases in apoptotic markers from baseline to time of surgery [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and 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 an increase in apoptotic cells measuring TUNNEL and caspase 3 expression. Positive response: difference higher than 30%.

  • Measurable changes in signaling pathways downstream PR [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and surgery) ]
    MFP action will be measured evaluating the expression of downstream markers related to PR activation such as CCND1, MYC, pSTAT5 and other proteins by immunohistochemistry. Positive response: differences higher than 30%


Other Outcome Measures:
  • Changes in tumor size [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and surgery) ]
    Measured by ecographic imaging. Twenty per cent of decrease in overall tumor size will be considered as a significant change.

  • RNAseq analysis of gene expression [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and surgery) ]
    Differences in gene expression between biopsy core and surgery sample higher than 20 % will be considered as an effective drug response.

  • Measure serum Mifepristone levels after 14 days Mifepristone treatment [ Time Frame: Baseline to time of surgery (14 days of treatment between biopsy core and surgery) ]
    Levels of Mifepristone will be measured by HPLC in the blood sample after treatment and correlate these levels with response to treatment (outcome 1).


Estimated Enrollment: 20
Actual Study Start Date: April 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mifepristone
Tablets of Mifepristone 200 mg p.o. once a day during 14 days between biopsy and surgery after confirming inclusion criteria
Drug: Mifepristone

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.

Other Name: RU-486

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion criteria

    1. Postmenopausal women (one year after menses stop)
    2. Confirmed diagnosis of breast cancer
    3. Tumors with higher expression PR > 50 % measured by IHC and PRA/RPB ratio equal or higher than 1.5 measured by WB
    4. All clinical stages with tumor size greater than 1.5 cm to allow obtaining material from biopsy cores
    5. 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

Exclusion Criteria:

  • Exclusion criteria

    1. Patients with no recommended surgery
    2. Patients which have received any other treatment for this cancer
    3. Patients expressing ER but expressing PRA/PRB levels lower than 1.5
    4. Hepatitis infection (HBV o HCV)
    5. HIV infection
    6. Cognitive alterations which limit the understanding of the protocol or compliance to the protocol
    7. Prolonged QT/QTc basal interval
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02651844


Contacts
Contact: Hugo D Gass, MD +54-11-4736-0211 ext 263 hugogass@fibertel.com.ar
Contact: Marcos Liguori, MD +54-11-4736-0211 ext 263 marquitosliguori@gmail.com

Locations
Argentina
Hospital Provincial Magdalena V de Martínez Recruiting
General Pacheco, Buenos Aires, Argentina, 1617
Contact: Hugo D Gass, MD    +54-11-4736-0211 ext 263    hugogass@fibertel.com.ar   
Contact: Marcos Liguori, MD    +54-11-4736-0211 ext 263    marquitosliguori@gmail.com   
Sponsors and Collaborators
Hospital Provincial Magdalena V. de Martínez
Agencia Nacional de Promoción de Ciencia y Tecnología, MINCYT
Instituto de Biología y Medicina Experimental (IBYME-CONICET)
Investigators
Study Director: Claudia Lanari, PhD IBYME-CONICET
  More Information

Publications:

Responsible Party: Hospital Provincial Magdalena V. de Martínez
ClinicalTrials.gov Identifier: NCT02651844     History of Changes
Other Study ID Numbers: PIDC-2012-0084
First Submitted: January 4, 2016
First Posted: January 11, 2016
Last Update Posted: June 12, 2017
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Hospital Provincial Magdalena V. de Martínez:
Progesterone receptor isoforms
Antiprogestins
Mifepristone
Neoadjuvant
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Progesterone
Mifepristone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents