Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: doxorubicin hydrochloride (Drug); enalapril maleate (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Masonic Cancer Center, University of Minnesota

Official(s) and/or principal investigator(s):
Anne H. Blaes, MD, Principal Investigator, Affiliation: Masonic Cancer Center, University of Minnesota

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 phase I trial is studying giving enalapril maleate together with doxorubicin hydrochloride to see how well it works in treating women with breast cancer.

Official title: The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment

Study design: Treatment, Randomized

Primary outcome: Increase or decrease in doxorubicin hydrochloride exposure

Secondary outcome:

Baseline and serial change in b-type natriuretic peptide, cardiac troponins, and urine microalbumin after infusion with doxorubicin hydrochloride

Effect of enalapril maleate on the formation of the doxorubicin hydrochloride metabolite, doxorubicinol

Effect of doxorubicin hydrochloride on intracellular leukocytes and platelets, in the presence and absence of enalapril maleate

Detailed description: OBJECTIVES:

Primary

- To determine if doxorubicin hydrochloride exposure is increased or decreased with

concurrent treatment with doxorubicin hydrochloride and enalapril maleate in women with breast cancer.

Secondary

- To evaluate the baseline and serial changes in the levels of b-type natriuretic

peptide, cardiac troponins, and urine microalbumin after infusion with doxorubicin hydrochloride.

- To evaluate the effect of enalapril maleate on the formation of the doxorubicin

hydrochloride metabolite, doxorubicinol.

- To evaluate the effect of doxorubicin hydrochloride on intracellular leukocytes and

platelets, in the presence and absence of enalapril maleate.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

- Arm I: 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.

- Arm II: 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 1, patients receive oral enalapril maleate once daily until day 8 of course 1.

Blood and urine samples are collected periodically for pharmacokinetic studies by HPLC with fluorescence detection.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS:

- Tissue diagnosis of a breast carcinoma

- Planning adjuvant doxorubicin hydrochloride every 2 weeks as part of a chemotherapy

regimen

PATIENT CHARACTERISTICS:

- Total bilirubin normal

- AST and ALT normal

- Creatinine clearance > 60 mL/min

- Not pregnant or nursing

- No known allergy to enalapril maleate

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 1 week since prior and no concurrent herbal supplements

- No concurrent P450 cytochrome inducers or inhibitors

- No concurrent grapefruit juice

- No concurrent angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor

blocker

University of Minnesota Children's Hospital - Fairview, Minneapolis, Minnesota 55455, United States; Recruiting
Clinical Trials Office - University of Minnesota Children's Ho, Phone: 612-273-3000

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: April 2009
Last updated: May 7, 2009