Clinical trial NCT01372644: Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor: A Proof of Principle Trial
Official title: Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor: A Proof of Principle Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atypical Ductal Breast Hyperplasia
Lobular Carcinoma in Situ (LCIS)
Atypical Lobular Hyperplasia (ALH) of Breast
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2011-06-14
Enrollment: 15
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cell Proliferation and apoptosis
timeFrame: 10 days
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU School of Medicine
state: New York
Study officials:
affiliation: NYU School of Medicine
name: David L Kleinberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU School of Medicine
name: Julia Smith, MD
role: STUDY_DIRECTOR
affiliation: NYU School of Medicine
name: Deborah Axelrod, MD
role: STUDY_DIRECTOR
References:
citation: Singh B, Smith JA, Axelrod DM, Ameri P, Levitt H, Danoff A, Lesser M, de Angelis C, Illa-Bochaca I, Lubitz S, Huberman D, Darvishian F, Kleinberg DL. Insulin-like growth factor-I inhibition with pasireotide decreases cell proliferation and increases apoptosis in pre-malignant lesions of the breast: a phase 1 proof of principle trial. Breast Cancer Res. 2014 Nov 11;16(6):463. doi: 10.1186/s13058-014-0463-1.