Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

University of Minnesota (UMN)

Status: Completed

Conditions: Breast Cancer

Treatments: Drug: doxorubicin hydrochloride; Drug: enalapril maleate

Study type: Interventional

Funder types: Other

Identifiers

NCT00895414

0806M34981 (Other Identifier)

2008NTLS060

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

19 participants in 2 patient groups

Doxorubicin alone first, then Doxorubicin with Enalapril

Experimental group

Description:

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.

Treatment:

Drug: enalapril maleate

Drug: doxorubicin hydrochloride

Doxorubicin with Enalapril first, then Doxorubicin alone

Experimental group

Description:

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.

Treatment:

Drug: enalapril maleate

Drug: doxorubicin hydrochloride