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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

May 7, 2009
March 4, 2014
April 2009
December 2014   (final data collection date for primary outcome measure)
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.
Increase or decrease in doxorubicin hydrochloride exposure [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00895414 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
Not Provided
 
Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer
The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • 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 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.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: enalapril maleate
  • 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.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: enalapril maleate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
17
December 2014
December 2014   (final data collection date for primary outcome measure)

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)
Female
18 Years and older
No
Contact: Anne Blaes, MD 612-624-0123 blaes004@umn.edu
United States
 
NCT00895414
2008NTLS060, 0806M34981
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Anne H. Blaes, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP