Trial Outcomes & Findings for Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer (NCT NCT00290732)
NCT ID: NCT00290732
Last Updated: 2013-10-31
Results Overview
Maximum tolerated dose (MTD) of administering pegylated liposomal doxorubicin (PLD) into one duct of women with breast cancer awaiting mastectomy. MTD reflects highest dose of drug that did not cause Dose Limiting Toxicity (DLT) in more than 30% of patients.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Until up to 30 days after PLD administration
Results posted on
2013-10-31
Participant Flow
From February 2006 to October 2009, 19 women signed consent, and 17 women were enrolled in the intraductal portion of the study. An addition 3 women receiving standard intravenous PLD were enrolled in a pharmacokinetic contract portion.
Participants were not included after consent if eligibility criteria were not met (eg, lab values, performance status); an additional 2 subjects were consented but not included in the study population.
Participant milestones
| Measure |
Intraductal Arm- 0 mg PLD
Participants received intraductal administration of dextrose prior to conventional surgery for breast cancer.
|
Intraductal Arm- 2 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 5 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 10 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.
|
Intravenous Arm
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
4
|
6
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Intraductal Arm- 0 mg PLD
Participants received intraductal administration of dextrose prior to conventional surgery for breast cancer.
|
Intraductal Arm- 2 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 5 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 10 mg PLD
Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.
|
Intravenous Arm
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
|---|---|---|---|---|---|
|
Overall Study
Inability to instill drug intraductally.
|
0
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer
Baseline characteristics by cohort
| Measure |
Intraductal Arm
n=17 Participants
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
|
Intravenous Arm
n=3 Participants
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
3 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Until up to 30 days after PLD administrationPopulation: Participants received intraductal administration of dextrose prior to conventional surgery for breast cancer.
Maximum tolerated dose (MTD) of administering pegylated liposomal doxorubicin (PLD) into one duct of women with breast cancer awaiting mastectomy. MTD reflects highest dose of drug that did not cause Dose Limiting Toxicity (DLT) in more than 30% of patients.
Outcome measures
| Measure |
Intraductal Arm
n=15 Participants
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
|
Intraductal Arm- 2 mg PLD
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 5 mg PLD
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 10 mg PLD
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.
|
Intravenous Arm
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
10 milligrams
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsyPopulation: Participants in whom blood and/or tissue samples were collected at surgery or breast biopsy.
Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in blood (plasma) across all the participants in each group is reported.
Outcome measures
| Measure |
Intraductal Arm
n=3 Participants
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
|
Intraductal Arm- 2 mg PLD
n=3 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 5 mg PLD
n=3 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 10 mg PLD
n=6 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.
|
Intravenous Arm
n=3 Participants
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
|---|---|---|---|---|---|
|
Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery
Doxorubicin, max
|
0 nM
Interval 0.0 to 0.0
|
28.5 nM
|
18.3 nM
|
902.0 nM
|
79300 nM
|
|
Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery
Doxorubicinol, max
|
0 nM
|
0 nM
|
0 nM
|
36.9 nM
|
8090 nM
|
SECONDARY outcome
Timeframe: Day of surgery/biopsyPopulation: Participants in whom blood and/or tissue samples were collected at surgery or breast biopsy.
Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in tissue across all the participants in each group is reported.
Outcome measures
| Measure |
Intraductal Arm
n=3 Participants
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
|
Intraductal Arm- 2 mg PLD
n=3 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 5 mg PLD
n=3 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.
|
Intraductal Arm- 10 mg PLD
n=6 Participants
Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.
|
Intravenous Arm
n=3 Participants
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
|---|---|---|---|---|---|
|
Concentrations of Doxorubicin in Tissue at Definitive Surgery
Doxorubicinol, max
|
0 nmol/g
|
0 nmol/g
|
0.09 nmol/g
|
5.26 nmol/g
|
0 nmol/g
|
|
Concentrations of Doxorubicin in Tissue at Definitive Surgery
Doxorubicin, max
|
0 nmol/g
|
0 nmol/g
|
1.73 nmol/g
|
10.82 nmol/g
|
0.21 nmol/g
|
Adverse Events
Intraductal Arm- 0 mg PLD
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Intraductal Arm- 2 mg PLD
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Intraductal Arm- 5 mg PLD
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Intraductal Arm- 10 mg PLD
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Intravenous Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Intraductal Arm- 0 mg PLD
n=3 participants at risk
|
Intraductal Arm- 2 mg PLD
n=3 participants at risk
|
Intraductal Arm- 5 mg PLD
n=3 participants at risk
|
Intraductal Arm- 10 mg PLD
n=6 participants at risk
|
Intravenous Arm
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Dermatology other (right areolar eschar)
|
0.00%
0/3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
0.00%
0/3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
0.00%
0/3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
16.7%
1/6 • Number of events 1 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
—
0/0 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
Other adverse events
| Measure |
Intraductal Arm- 0 mg PLD
n=3 participants at risk
|
Intraductal Arm- 2 mg PLD
n=3 participants at risk
|
Intraductal Arm- 5 mg PLD
n=3 participants at risk
|
Intraductal Arm- 10 mg PLD
n=6 participants at risk
|
Intravenous Arm
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
|---|---|---|---|---|---|
|
Reproductive system and breast disorders
Breast fullness
|
100.0%
3/3 • Number of events 3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
100.0%
3/3 • Number of events 3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
66.7%
2/3 • Number of events 2 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
16.7%
1/6 • Number of events 1 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
—
0/0 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
|
Reproductive system and breast disorders
Breast or nipple pain/discomfort
|
66.7%
2/3 • Number of events 2 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
100.0%
3/3 • Number of events 3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
100.0%
3/3 • Number of events 3 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
100.0%
6/6 • Number of events 6 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
—
0/0 • After definitive surgery
Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.
|
Additional Information
Dr. Vered Stearns
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phone: 4432876489
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place