Female Breast Carcinoma, Female Ductal Carcinoma In Situ
Conditions
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.
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.
Interventions
DRUGFulvestrant
Sponsors
Atossa Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intramuscular Fulvestrant 500mg fulvestrant administered intramuscularly
Fulvestrant | 2 |
| Intraductal Fulvestrant up to 500mg fulvestrant administered intraductally
Fulvestrant | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Intraductal Fulvestrant | Total | Intramuscular Fulvestrant |
|---|---|---|---|
| Age, Continuous | 45 years | 60 years | 67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 1 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Safety and Tolerability of Two Delivery Methods
Number of adverse events per CTCAE v4.0 after treatment with fulvestrant by route of administration
Time frame: Up to 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intramuscular Route | Safety and Tolerability of Two Delivery Methods | 1 Participants |
| Intraductal Route | Safety and Tolerability of Two Delivery Methods | 0 Participants |