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

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

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.

Study Overview

• Status: Terminated
• Conditions: Female Breast Carcinoma; Female Ductal Carcinoma In Situ
• Intervention / Treatment: Drug: Fulvestrant

Detailed Description

This is an open-label, non-randomized pharmacokinetic study of pre-surgical fulvestrant in women scheduled for mastectomy or lumpectomy. Eligible subjects will be identified upon admission to the institution for surgical management of breast cancer or DCIS, specifically mastectomy or lumpectomy. There will be 5 groups, each consisting of 6 subjects. The first subject of each group will receive fulvestrant administered intramuscularly and the next 5 subjects will receive fulvestrant intraductally. Subjects where at least 1 suitable duct is identified may undergo nipple aspiration in order to facilitate duct identification and intraductal infusion of a fulvestrant accompanied by imaging (saline+ ultrasound). A maximum of 5 ducts will receive intraductal infusion of fulvestrant. Across all ducts, the total dose will not exceed 500 mg (10 mL). All subjects will be monitored for systemic and local adverse events during the procedure, immediately following the procedure, within 30 minutes, 1 hour, 4 hours and by phone following discharge on Days +1 and +2, +7, and pre-operative. Subsequent to mastectomy or lumpectomy, subjects will be assessed for systemic adverse events until discharge. Subjects that receive fulvestrant will undergo serial blood draws to determine fulvestrant blood concentration levels.

This study was terminated due to revised commercial analyses including a review of the potential to enroll in a timely manner the planned number of patients. This study was not terminated because of safety or efficacy concerns.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • The Johns Hopkins School of Medicine
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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
4. Pathological diagnosis of Invasive Ductal Breast Cancer or Ductal Carcinoma in Situ requiring mastectomy or lumpectomy
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 100 days post study drug administration.

Exclusion Criteria:

1. Concurrent treatment with another anti-estrogen
2. Presence of an active infection requiring systemic therapy

3. The following conditions contra-indicating fulvestrant administration:

   1. Subjects with bleeding diatheses, thrombocytopenia or current anticoagulant use (excluding aspirin and anti-inflammatories)
   2. Subjects with a known hypersensitivity to fulvestrant or any of its formulation components including castor oil, alcohol, benzyl alcohol, and benzyl benzoate.
   3. Severe hepatic impairment.
4. Prior surgery on the ipsilateral breast which interrupts communication of the ductal systems with the nipple
5. Prior radiation to the breast
6. Pregnant or lactating
7. Impaired cardiac function or history of cardiac problems of NYHA Class 111 and IV
8. Poor nutritional state as indicated by a BMI below 20.
9. Presence of serious infection not controlled with systemic therapy
10. History of allergies to Lidocaine or Novocain
11. Concurrent participation in an experimental drug study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intramuscular Fulvestrant; 500mg fulvestrant administered intramuscularly	Drug: Fulvestrant; Other Names: Faslodex
Experimental: Intraductal Fulvestrant; up to 500mg fulvestrant administered intraductally	Drug: Fulvestrant; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Two Delivery Methods	Number of adverse events per CTCAE v4.0 after treatment with fulvestrant by route of administration	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Atossa Therapeutics, Inc.
• Investigators: Study Chair: Steven C Quay, Atossa Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): August 13, 2020

Study Registration Dates

• First Submitted: August 28, 2015
• First Submitted That Met QC Criteria: September 1, 2015
• First Posted (Estimated): September 3, 2015

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: ATOS-2015-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No