Breast Cancer Chemoprevention by SOM230, an IGF-I Action Inhibitor

• Status: Terminated
• Trial end date: 2015-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

This will be a proof of principle clinical trial to evaluate the use of pasireotide (SOM230) in women with ductal carcinoma in situ (DCIS) of the breast. Surgery and radiotherapy are used as treatment for DCIS and subsequent treatment with antiestrogens has been effective in reducing the occurrence of invasive breast cancer. Unfortunately, treatment with antiestrogens carries potential serious side effects and toxicities that are intolerable to some patients. Preliminary data suggest that inhibition of IGF-1 action in the breast will be at least as effective as tamoxifen. Pasireotide is a somatostatin analog that prevents mammary development by inhibiting IGF-1 action directly in the mammary gland and also indirectly without causing menopausal symptoms. This study is an expansion of work that we have previously done in women with atypical hyperplasia of the breast, which showed that treatment with pasireotide for 10 days caused a reduction in the cellularity of these precancerous lesions. In our present study, women with DCIS will be treated with pasireotide for 20 days prior to surgical excision. Endpoints will be as follows:

1. To determine whether pasireotide will inhibit cell proliferation and angiogenesis (signs of tumor growth), and stimulate apoptosis (cell death) in surgically excised tissue in comparison to core biopsies from women with estrogen receptor (ER) positive DCIS. Both the core biopsy and surgical excision are standard of care procedures that women with DCIS have regardless of participation in this trial.

2. To use dynamic contrast enhanced MRI to assess patients before and after treatment with pasireotide and evaluate for changes in tumor volume and other tumor related features

3. In our previous study we found that many women experienced a slight elevation in blood sugar with 10 days of treatment with pasireotide. Other work has shown that this effect often resolves with greater duration of treatment. We are therefore expanding the duration of treatment in this study to 20 days to assess if the initial hyperglycemia seen with pasireotide improves as treatment duration progresses.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Treatments: Pasireotide

Criteria

Inclusion Criteria:

• 21 years of age and older

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

• The participant has breast biopsy consistent with Ductal Carcinoma in situ (DCIS)

• 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 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 for 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 pasireotide

• Pregnancy: All subjects will have a beta-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 either by history or by HgbA1c greater than 6.5% or fasting serum glucose greater than 100mg/dL on screening labs. If fasting serum glucose is greater than 100mg/dL on screening labs, this test will be repeated to confirm the results

• Inability to inject medication or test for finger stick glucose

• Gall bladder disease

• History of cholecystitis without cholecystectomy

• Electrolyte abnormalities (particularly hypokalemia or hypomagnesemia)

• Contraindication for MRI

• If tumor size is < 1cm on mammography and all calcifications are removed on core biopsy the patient will be excluded.

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.

Hepatic Related Exclusion Criteria

• Baseline Alanine transaminase (ALT) or Aspartate transaminase (AST) > 2x upper limit of normal (ULN) without known complications of metastatic liver disease or primary hepatic disease (e.g. Cushing's disease and Acromegaly studies).

• Baseline Total Bilirubin > 1.5x ULN