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| ID | Type | Description | Link |
|---|---|---|---|
| 0806M34981 | Other Identifier | IRB, University of Minnesota |
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RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Enalapril maleate may help protect heart cells from the side effects of chemotherapy. It is not yet known whether giving enalapril maleate before or after doxorubicin hydrochloride is more effective in treating women with breast cancer.
PURPOSE: This randomized clinical trial is studying giving enalapril maleate together with doxorubicin hydrochloride to see how well it works in treating women with breast cancer.
This study is a drug interaction study designed to study the effects of enalapril on doxorubicin metabolism. Women with breast cancer for whom at least two cycles every 14 day doxorubicin is planned will be considered for enrollment. Study participation will be for 2 treatment cycles of doxorubicin or approximately 4 weeks. Patients will receive a 14 day course of daily enalapril in association with one cycle of doxorubicin and receive no study agent during the other cycle allowing patients to act as their own control. The sequence of enalapril dosing will be assigned by randomization at study enrollment. Blood samples for pharmacokinetics will be drawn before and at 7 time points after each of the two doses of doxorubicin. For each patient, serum doxorubicin and doxorubicinol concentrations both on and off of enalapril will be compared.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxorubicin alone first, then Doxorubicin with Enalapril | Experimental | Patients receive doxorubicin hydrochloride IV over 5-10 minutes 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 also receive oral enalapril maleate once daily until day 8 of course 2. |
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| Doxorubicin with Enalapril first, then Doxorubicin alone | Experimental | 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 receive oral enalapril maleate once daily until day 8 of course 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| doxorubicin hydrochloride | Drug | Given IV 5-10 minutes on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Tissue diagnosis of a breast carcinoma
The oncologist must have prescribed doxorubicin as part of the planned chemotherapy regimen
Have acceptable organ function within 14 days of enrollment defined as:
At least 18 years old
Patient must have given written informed consent indicating an understanding of the investigational nature of the study
Agrees not to consume grapefruit juice while on the study
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne H. Blaes, MD | Masonic Cancer Center, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States | ||
| University of Minnesota Children's Hospital - Fairview |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (14 Days) |
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| Second Intervention (14 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Patients who were randomized to receive either doxorubicin hydrochloride alone or doxorubicin hydrochloride with enalapril. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Number | participants | Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin |
|
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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."
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| tingling | Nervous system disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Anne Blaes | Masonic Cancer Center, University of Minnesota | 612-626-8138 | blaes004@umn.edu |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| D004656 | Enalapril |
| D015773 | Enalaprilat |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
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|
| enalapril maleate | Drug | Given orally - Beginning 1 week before course 2, patients also receive oral enalapril maleate once daily until day 8 of course 2. OR Beginning 1 week before course 1, patients receive oral enalapril maleate once daily until day 8 of course 1. |
|
|
| Baseline, 4, 24 and 48 hours after infusion of doxorubicin |
| The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril | Doxorubicin is metabolized to doxorubicinol. The effects of enalapril on doxorubicinol will be assessed. Statistical significance defined as a p < 0.05. | Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin |
| Minneapolis |
| Minnesota |
| 55455 |
| United States |
| NOT COMPLETED |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants who received doxorubicin hydrochloride with enalapril in either Cycle 1 or Cycle 2. |
|
|
| Secondary | 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 | 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. | Posted | Count of Participants | Participants | Baseline, 4, 24 and 48 hours after infusion of doxorubicin |
|
|
|
| Secondary | The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril | Doxorubicin is metabolized to doxorubicinol. The effects of enalapril on doxorubicinol will be assessed. Statistical significance defined as a p < 0.05. | Posted | Count of Participants | Participants | Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin |
|
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|
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | 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. | 0 | 9 | 2 | 9 |
| lightheaded | Nervous system disorders |
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| dizziness | Nervous system disorders |
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| cough | Respiratory, thoracic and mediastinal disorders |
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| headache | Nervous system disorders |
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| rash | Skin and subcutaneous tissue disorders |
|
| chest pain, NOS | Gastrointestinal disorders |
|
| fatigue | General disorders |
|
| palpitations | Cardiac disorders |
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| food poisoning | Gastrointestinal disorders |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |