Clinical trial NCT00895414: Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer
Official title: The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2009-05-08
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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:

  * liver function: total bilirubin, AST and ALT within normal institutional limits
  * kidney function: estimated Creatinine Clearance \> 60 ml/min calculated creatinine clearance (for females) - formula: (140 - age) x weight x .85 divided by (sCr x 72)
* 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:

* Known allergy to enalapril
* Taking any known P450 cytochrome inducers or inhibitors
* Taking any herbal supplements while on the study or the week prior to receiving doxorubicin
* Taking an ace-inhibitor or angiotensin receptor blocker
* Pregnant or lactating. Enalapril is Pregnancy Categories C (first trimester) and D (second and third trimesters)

Primary outcomes:
measure: 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.
timeFrame: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin
Secondary outcomes:
measure: 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
timeFrame: Baseline, 4, 24 and 48 hours after infusion of doxorubicin
measure: The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril
timeFrame: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin
Other outcomes:
Locations:
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Children's Hospital - Fairview
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Anne H. Blaes, MD
role: PRINCIPAL_INVESTIGATOR
References: