Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor: A Proof of Principle Trial

Atypical Ductal Breast Hyperplasia Clinical Trial

Official title:

Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor: A Proof of Principle Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01372644
• Other study ID #: R6-937
• Secondary ID: BC061512
• Status: Completed
• Phase: Phase 1
• First received: June 9, 2011
• Last updated: December 2, 2016
• Start date: November 2007
• Est. completion date: November 2013

Study information

• Verified date: December 2016
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) increases breast cancer risk. In post menopausal women, SERMS are standard chemopreventive agents. The investigators have previously shown insulin-like growth factor-I (IGF-I) is required to permit estrogen (E2) and progesterone action in the mammary gland, and that a novel somatostatin analog, SOM230, that inhibits IGF-I action can prevent E2 action on the mammary gland. It reduces cell proliferation and increases apoptosis (cell death) in the rat mammary gland. This study was designed to determine whether women at high risk for breast cancer respond to SOM230 in the same way that rats do. Methods: Women with atypical ductal hyperplasia or lobular carcinoma in-situ by core biopsy were treated for 9.5 days with SOM230 (600mcg BID). Surgical excision was performed on day 10. Sections were examined before and after SOM230 treatment for cell proliferation (Ki67) and apoptosis (TUNEL). Serum IGF-I, fasting glucose, insulin, and HbA1C were measured in anticipation of changes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 2013
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years and older

Eligibility

Inclusion Criteria

• Over 21 years of age

• Must sign informed consent, witnessed, and dated prior to entry

• The participant has an increased risk for developing breast cancer which may include; Atypical Ductal Hyperplasia (ADH), Lobular Carcinoma in situ (LCIS), and/or Atypical Lobular Hyperplasia (ALH)

• Performance Status: ECOG 0-1 unless mobility is limited from chronic physical handicap

• No clinical evidence of other malignancies (except Basal Cell carcinoma)

• Complete blood count, differential and platelet count must be within normal limits (WNL) or verified by the study chair to be related to conditions not interfering with normal health status

• Adequate hepatic and renal function (these must be WNL or verified by study chair to be related to conditions not interfering with normal health status)

• Normal fasting glucose

• No history of diabetes

• Medically and Psychologically able to comply with all study requirements

• Accessible to Follow up

Exclusion Criteria

• Less than 21 years of age

• Known invasive breast cancer of any type

• Bilateral prophylactic mastectomy

• Prior malignancy of any type that occurred less than 5 years previously, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

• Existing non-malignant disease that would preclude the administration of SOM230

• Pregnancy: All subjects will have a beta human chorionic gonadotropin (b-hCG) serum pregnancy test to rule out pregnancy, a history will also be taken to make certain that recent sexual exposure does not put them at risk for pregnancy. If so a second serum pregnancy test will be done. Volunteers will be asked to use barrier contraception during study.

• Tamoxifen or other preventive measures within 6 months

• Serious Psychiatric condition or addictive disorder

• Diabetes or elevated fasting blood sugar

• Inability to inject medication or test for finger stick glucose

• Symptomatic gallstones or known gall bladder disease

• History of cholecystitis without cholecystectomy

• Electrolyte abnormalities (particularly hypokalemia or hypomagnesemia)

QT related exclusion criteria

• QTcF at screening > 450 msec.

• History of syncope or family history of idiopathic sudden death.

• Sustained or clinically significant cardiac arrhythmias.

• Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block.

• Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure

• Concomitant medication(s) known to increase the QT interval.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atypical Ductal Breast Hyperplasia
• Atypical Lobular Hyperplasia (ALH) of Breast
• Carcinoma in Situ
• Carcinoma, Lobular
• Hyperplasia
• Lobular Carcinoma in Situ (LCIS)

Intervention

Drug:
• SOM 230 / Pasireotide

Locations

Country	Name	City	State
United States	NYU School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell Proliferation and apoptosis	Tissue from initial diagnostic breast biopsies will be compared to the remaining tissue excised after treatment with SOM230. Tissue will be stained to measure cell proliferation and apoptosis (cell death).	10 days	No