Trial Outcomes & Findings for Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer (NCT NCT00895414)

Last Updated: 2019-05-08

Results Overview

Doxorubicin plasma concentration (DPC) is the primary pharmacokinetic (PK) measure of the exposure. Each patient will have serial PKs performed twice - once with enalapril and once without enalapril. A mean increase or decrease of more than 115 ng/ml in DPC will be considered significant.

Recruitment status

COMPLETED

Study phase

Target enrollment

19 participants

Primary outcome timeframe

Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin

Results posted on

2019-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	Doxorubicin Alone First, Then Doxorubicin With Enalapril Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 2, patients additionally receive oral enalapril maleate once daily until day 8 of course 2.	Doxorubicin With Enalapril First, Then Doxorubicin Alone Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 1, patients additionally receive oral enalapril maleate once daily until day 8 of course 1.
First Intervention (14 Days) STARTED	9	10
First Intervention (14 Days) COMPLETED	8	9
First Intervention (14 Days) NOT COMPLETED	1	1
Second Intervention (14 Days) STARTED	8	9
Second Intervention (14 Days) COMPLETED	8	9
Second Intervention (14 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Doxorubicin Alone First, Then Doxorubicin With Enalapril Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 2, patients additionally receive oral enalapril maleate once daily until day 8 of course 2.	Doxorubicin With Enalapril First, Then Doxorubicin Alone Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 1, patients additionally receive oral enalapril maleate once daily until day 8 of course 1.
First Intervention (14 Days) Withdrawal by Subject	1	0
First Intervention (14 Days) Physician Decision	0	1

Baseline Characteristics

Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=19 Participants Patients who were randomized to receive either doxorubicin hydrochloride alone or doxorubicin hydrochloride with enalapril.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin

Outcome measures

Outcome measures
Measure	Doxorubicin Hydrochloride Alone n=17 Participants Participants who received doxorubicin hydrochloride alone in either Cycle 1 or Cycle 2.	Doxorubicin Hydrochloride With Enalapril n=17 Participants Participants who received doxorubicin hydrochloride with enalapril in either Cycle 1 or Cycle 2.
Number of Patients With Doxorubicin Plasma Concentrations Demonstrating a Significant Increase or Decrease When Doxorubicin Was Given With Enalapril as Compared to When Doxorubicin Was Given Without Enalapril.	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 4, 24 and 48 hours after infusion of doxorubicin

Doxorubicin can induce changes in troponin, b-type natriuretic peptide and urine microalbumin. This analysis will determine whether enalapril prevents any of these changes. Statistical significance defined as a p \< 0.05.

Outcome measures

Outcome measures
Measure	Doxorubicin Hydrochloride Alone n=17 Participants Participants who received doxorubicin hydrochloride alone in either Cycle 1 or Cycle 2.	Doxorubicin Hydrochloride With Enalapril n=17 Participants Participants who received doxorubicin hydrochloride with enalapril in either Cycle 1 or Cycle 2.
The Number of Participants With a Significant Increase or Decrease in the Baseline Levels of Btype Natriuretic Peptide, Cardiac Troponins, and Urine Microalbumin With or Without Enalapril	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin

Doxorubicin is metabolized to doxorubicinol. The effects of enalapril on doxorubicinol will be assessed. Statistical significance defined as a p \< 0.05.

Outcome measures

Outcome measures
Measure	Doxorubicin Hydrochloride Alone n=17 Participants Participants who received doxorubicin hydrochloride alone in either Cycle 1 or Cycle 2.	Doxorubicin Hydrochloride With Enalapril n=17 Participants Participants who received doxorubicin hydrochloride with enalapril in either Cycle 1 or Cycle 2.
The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril	0 Participants	0 Participants

Adverse Events

Doxorubicin Alone First, Then Doxorubicin With Enalapril

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Doxorubicin With Enalapril First, Then Doxorubicin Alone

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Doxorubicin Alone First, Then Doxorubicin With Enalapril n=8 participants at risk Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 2, patients additionally receive oral enalapril maleate once daily until day 8 of course 2.	Doxorubicin With Enalapril First, Then Doxorubicin Alone n=9 participants at risk Patients receive doxorubicin hydrochloride IV on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week before course 1, patients additionally receive oral enalapril maleate once daily until day 8 of course 1.
Nervous system disorders tingling	0.00% 0/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	11.1% 1/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Nervous system disorders lightheaded	0.00% 0/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	11.1% 1/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Nervous system disorders dizziness	37.5% 3/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Respiratory, thoracic and mediastinal disorders cough	12.5% 1/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Nervous system disorders headache	0.00% 0/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	11.1% 1/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Skin and subcutaneous tissue disorders rash	0.00% 0/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	11.1% 1/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Gastrointestinal disorders chest pain, NOS	12.5% 1/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
General disorders fatigue	12.5% 1/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Cardiac disorders palpitations	12.5% 1/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."
Gastrointestinal disorders food poisoning	12.5% 1/8 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."	0.00% 0/9 The adverse events could not be reported per intervention because the arms themselves were designed originally as one being "Doxorubicin Alone First, Then Doxorubicin With Enalapril" and the other being "Doxorubicin With Enalapril First, Then Doxorubicin Alone." As such the data was collected and reported under these two arms and it would not be possible further separate the adverse events by "Doxorubicin Hydrochloride Alone" and "Doxorubicin Hydrochloride With Enalapril."

Additional Information

Dr. Anne Blaes

Masonic Cancer Center, University of Minnesota

Phone: 612-626-8138

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place