A Pre-Surgical PK Study of IM and Intraductally Delivered Fulvestrant (007)

• ClinicalTrials.gov Identifier: NCT02540330
• Recruitment Status: Recruiting
• First Posted: September 3, 2015
• Last Update Posted: October 15, 2019
• Sponsor: Atossa Genetics, Inc.
• Information provided by (Responsible Party): Atossa Genetics, Inc.

Study Description

Brief Summary:

This is an open-label, non-randomized pharmacokinetic study of fulvestrant in women scheduled for mastectomy or lumpectomy. Eligible subjects will be identified with breast cancer or DCIS. The first subject of each of five groups will receive fulvestrant intramuscularly. The subsequent 5 subjects of each group will receive fulvestrant by intraductal instillation. All subjects will be monitored for systemic and local adverse events during the procedure, and following the procedure until mastectomy or lumpectomy. Subjects that receive fulvestrant will undergo serial blood draws to determine fulvestrant blood concentration levels.

Condition or disease	Intervention/treatment	Phase
Female Breast Carcinoma; Female Ductal Carcinoma In Situ	Drug: Fulvestrant	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Phase 2 Pharmacokinetic Study of Pre-Surgical Intramuscular and Intraductal Fulvestrant in Women With Invasive Breast Cancer or DCIS Undergoing Mastectomy or Lumpectomy
• Actual Study Start Date: March 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Intramuscular Fulvestrant; 500mg fulvestrant administered intramuscularly	Drug: Fulvestrant; Other Name: Faslodex
Experimental: Intraductal Fulvestrant; up to 500mg fulvestrant administered intraductally	Drug: Fulvestrant; Other Name: Faslodex

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability of Two Delivery methods [ Time Frame: Up to 4 weeks ]
   Compare the number and severity of adverse events per CTCAE v4.0
2. Compare the pathological effects between the 2 routes of administration [ Time Frame: Up to 4 weeks ]
   Determine the pathological effects, specifically changes in Ki67, ER/PgR expression between the pre-fulvestrant biopsy and the post-fulvestrant surgical specimen.

Secondary Outcome Measures :

1. Compare fulvestrant levels by route of administration [ Time Frame: Up to 4 weeks ]
   Compare the tissue and circulating levels of fulvestrant following a single dose administered either intramuscularly or intraductallly

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female
2. 18 years of age or older
3. Scheduled to undergo non-nipple sparing mastectomy for Invasive Breast Cancer or DCIS within 1 month
4. Pathological diagnosis of Invasive Ductal Breast Cancer or Ductal Carcinoma in Situ requiring mastectomy
5. Estrogen Receptor-positive pathology
6. ECOG performance scale of 0-1

7. Adequate organ function as defined by the following criteria:

   • Absolute neutrophil count (ANC) ≥ 1500/μl
   • Platelets ≥ 100,000/μl
   • Hemoglobin ≥ 9.0 g/dl
   • Creatinine ≤ 2 times upper limit of normal
   • Bilirubin ≤ 2 times upper limit of normal
   • Transaminases (AST/SGOT and ALT/SGPT) ≤ 2.5 times upper limit of normal
8. Able to sign informed consent
9. Willing to use effective contraception for at least 28-days post study drug administration.

Exclusion Criteria:

1. Diagnosis of inflammatory breast carcinoma
2. Concurrent treatment with another anti-estrogen
3. Presence of an infection including ulcerations and fungal infections in the breast to be studied

4. Any condition contraindicating fulvestrant administration:

   • Subjects with bleeding diatheses, thrombocytopenia or current anticoagulant use
   • Subjects with a known hypersensitivity to fulvestrant or any of its formulation components including castor oil, alcohol, benzyl alcohol, and benzyl benzoate.
   • Several hepatic impairments, define as Child-Pugh Class C or worse
5. Prior breast surgery which interrupts communication of the ductal systems with the nipple
6. Diagnosis of triple-negative or ER-negative breast cancer
7. Non-Ductal Pathology: Lobular or Colloid type presence
8. Subjects scheduled to undergo nipple sparing mastectomy
9. Prior radiation to the breast or chest wall
10. Pregnant or lactating
11. Impaired renal function
12. Impaired cardiac function or history of cardiac problems
13. Poor nutritional state (as determined by clinician)
14. Depressed bone marrow
15. Presence of serious infection
16. Presence of ascites (as determined by clinician)
17. Presence of pleural effusion
18. Allergies to Lidocaine or Novocain
19. Allergies to imaging dyes

Contacts and Locations

Contacts

Contact: Steven C Quay, MD, PhD; 206.419.4873; steven.quay@atossagenetics.com

Contact: Janet R Rea, MSPH; 206-799-7186; janet.rea@atossagenetics.com

Locations

United States, Maryland

The Johns Hopkins School of Medicine; Not yet recruiting

Baltimore, Maryland, United States, 21205

Contact: Lisa Jacobs, MD ljacob14@jhmi.edu

United States, New York

Montefiore Medical Center; Recruiting

New York, New York, United States, 10461

Contact: ameriangel M Roman 714-405-8578 aromaner@montefiore.org

Principal Investigator: Sheldon M Feldman, MD, FACS

Sponsors and Collaborators

Atossa Genetics, Inc.

More Information

• Responsible Party: Atossa Genetics, Inc.
• ClinicalTrials.gov Identifier: NCT02540330 History of Changes
• Other Study ID Numbers: ATOS-2015-007
• First Posted: September 3, 2015
• Last Update Posted: October 15, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Fulvestrant; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs