Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00895414

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: doxorubicin hydrochloride Drug: enalapril maleate	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Enalapril Enalapril maleate Enalaprilat

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Increase or decrease in doxorubicin hydrochloride exposure [ Designated as safety issue: No ]

Secondary Outcome Measures:

Baseline and serial change in b-type natriuretic peptide, cardiac troponins, and urine microalbumin after infusion with doxorubicin hydrochloride [ Designated as safety issue: No ]
Effect of enalapril maleate on the formation of the doxorubicin hydrochloride metabolite, doxorubicinol [ Designated as safety issue: No ]
Effect of doxorubicin hydrochloride on intracellular leukocytes and platelets, in the presence and absence of enalapril maleate [ Designated as safety issue: No ]

Estimated Enrollment:	17
Study Start Date:	April 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: 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.	Drug: doxorubicin hydrochloride Given IV Drug: enalapril maleate Given orally
Arm II: 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.	Drug: doxorubicin hydrochloride Given IV Drug: enalapril maleate Given orally

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895414

Locations

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

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Anne H. Blaes, MD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Anne H. Blaes )
Study ID Numbers:	CDR0000640914, UMN-2008NTLS060, 0806M34981
Study First Received:	May 7, 2009
Last Updated:	May 7, 2009
ClinicalTrials.gov Identifier:	NCT00895414 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Breast Neoplasms
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Antibiotics, Antineoplastic
Doxorubicin

Pharmacologic Actions
Protease Inhibitors
Neoplasms
Enalapril
Neoplasms by Site
Enalaprilat
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Breast Diseases

ClinicalTrials.gov processed this record on February 09, 2010