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

NCT01372618 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 10-00641BC097854
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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.

Conditions

Ductal Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• 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).

  Before and after 20 days of treatment

Secondary Outcomes (2)

• Effect of SOM 230 / Pasireotide on Tumor Volume and Tumor Kinetics

  Before and after 20 days of treatment

• Hyperglycemia

  Before and after 20 days of treatment with 3 month post-treatment follow-up

Study Arms (1)

SOM 230/Pasireotide

EXPERIMENTAL

Treatment with SOM230 600mcg twice daily for 20 days.

Drug: SOM 230 / Pasireotide

Interventions

SOM 230 / Pasireotide DRUG

SOM230/Pasireotide is a multi-receptor targeted somatostatin analogue. In this trial, 600 mcg of SOM230/Pasireotide are taken twice daily subcutaneously.

SOM 230/Pasireotide

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Results Point of Contact

• Title: David Kleinberg
• Organization: NYU Langone

david.kleinberg@nyumc.org

646 501 7504

Study Officials

• David L Kleinberg, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 14, 2011
• Study Start: June 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 27, 2017
• Results First Posted: December 27, 2017

Record last verified: 2017-11

Locations

US (1)