Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00895414
First received: May 7, 2009
Last updated: March 4, 2014
Last verified: March 2014
  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 clinical trial is studying giving enalapril maleate together with doxorubicin hydrochloride to see how well it works in treating women with breast cancer.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Increase or decrease in doxorubicin hydrochloride exposure [ Time Frame: Before and After Receiving Enalapril ] [ Designated as safety issue: No ]
    Doxorubicin plasma concentration (DPC) will be the primary pharmacokinetic (PK) measure of the exposure. Each patient will have PK performed twice - once with enalapril and once without enalapril. An increase of more than 115 ng/ml in DPC will be considered important.


Secondary Outcome Measures:
  • Change in b-type natriuretic peptide, cardiac troponins, and urine microalbumin after infusion with doxorubicin hydrochloride [ Time Frame: Before and After Treatment with Doxorubicin with and without Enalapril ] [ Designated as safety issue: No ]
    Doxorubicin can induce changes in troponin, b-type natriuretic peptide and urine microalbumin. This analysis will determine whether enalapril prevents any of these changes.

  • Effect of enalapril maleate on the formation of the doxorubicin hydrochloride metabolite, doxorubicinol [ Time Frame: Before and After Treatment with Doxorubicin with and without Enalapril ] [ Designated as safety issue: No ]
    Doxorubicin is metabolized to doxorubicinol. The efeects of enalapril on doxorubicinol will be assessed.


Estimated Enrollment: 17
Study Start Date: April 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: doxorubicin hydrochloride
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.
Other Name: Adriamycin
Drug: enalapril maleate
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.
Other Name: Vasotec
Experimental: Arm II
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 5-10 minutes on day 1. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Other Name: Adriamycin
Drug: enalapril maleate
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.
Other Name: Vasotec

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Anne Blaes, MD 612-624-0123 blaes004@umn.edu

Locations
United States, Minnesota
Fairview Southdale Hospital Recruiting
Edina, Minnesota, United States, 55435
University of Minnesota Children's Hospital - Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Nancy Youngren    612-626-2140    young025@umn.edu   
Principal Investigator: Anne Blaes, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Anne H. Blaes, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00895414     History of Changes
Other Study ID Numbers: 2008NTLS060, 0806M34981
Study First Received: May 7, 2009
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Maleic acid
Enalapril
Enalaprilat
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014