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

• Sponsor: Atossa Genetics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02540330
• Collaborator: (none)
• Enrollment: 3
• Locations: 2
• Arms: 2
• Actual Duration (Months): 53.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

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

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 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: Mar 1, 2016
• Actual Primary Completion Date: Aug 13, 2020
• Actual Study Completion Date: Aug 13, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Two Delivery Methods [Up to 4 weeks]

   Number of adverse events per CTCAE v4.0 after treatment with fulvestrant by route of administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

1. Able to sign informed consent

2. 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:

4. Subjects with bleeding diatheses, thrombocytopenia or current anticoagulant use (excluding aspirin and anti-inflammatories)

5. Subjects with a known hypersensitivity to fulvestrant or any of its formulation components including castor oil, alcohol, benzyl alcohol, and benzyl benzoate.

6. Severe hepatic impairment.

7. Prior surgery on the ipsilateral breast which interrupts communication of the ductal systems with the nipple

8. Prior radiation to the breast

9. Pregnant or lactating

10. Impaired cardiac function or history of cardiac problems of NYHA Class 111 and IV

11. Poor nutritional state as indicated by a BMI below 20.

12. Presence of serious infection not controlled with systemic therapy

13. History of allergies to Lidocaine or Novocain

14. Concurrent participation in an experimental drug study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Johns Hopkins School of Medicine	Baltimore	Maryland	United States	21205
2	Montefiore Medical Center	New York	New York	United States	10461

Sponsors and Collaborators

• Atossa Genetics, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 6, 2020

More Information

Publications

None provided.

• Responsible Party: Atossa Genetics, Inc.
• ClinicalTrials.gov Identifier: NCT02540330
• Other Study ID Numbers: ATOS-2015-007
• First Posted: Sep 3, 2015
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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; Fulvestrant

Study Results

Participant Flow

Arm/Group Title	Intramuscular Fulvestrant	Intraductal Fulvestrant
Arm/Group Description	500mg fulvestrant administered intramuscularly Fulvestrant	up to 500mg fulvestrant administered intraductally Fulvestrant
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intramuscular Fulvestrant	Intraductal Fulvestrant	Total
Arm/Group Description	500mg fulvestrant administered intramuscularly Fulvestrant	up to 500mg fulvestrant administered intraductally Fulvestrant	Total of all reporting groups
Overall Participants	2	1	3
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	67	45	60
Sex: Female, Male (Count of Participants)
Female	2 100%	1 100%	3 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 100%	1 33.3%
Not Hispanic or Latino	2 100%	0 0%	2 66.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 100%	0 0%	2 66.7%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 100%	1 33.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intramuscular Route	Intraductal Route
Arm/Group Description	500mg fulvestrant	up to 500mg fulvestrant
Measure Participants	2	1
Count of Participants [Participants]	1 50%	0 0%

Adverse Events

Time Frame	Up to 50 days
Arm/Group Title	Intramuscular Fulvestrant		Intraductal Fulvestrant
Arm/Group Description	500mg fulvestrant administered intramuscularly Fulvestrant		up to 500mg fulvestrant administered intraductally Fulvestrant
All Cause Mortality
	Intramuscular Fulvestrant		Intraductal Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Intramuscular Fulvestrant		Intraductal Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Intramuscular Fulvestrant		Intraductal Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Pain	1/2 (50%)	2	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.