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Trial record 17 of 2157 for:    doxorubicin

Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

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ClinicalTrials.gov Identifier: NCT00895414
Recruitment Status : Completed
First Posted : May 8, 2009
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Drug: doxorubicin hydrochloride Drug: enalapril maleate Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Enalapril on Doxorubicin Exposure in Adjuvant Breast Cancer Treatment
Study Start Date : April 2009
Actual Primary Completion Date : April 2014
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Doxorubicin alone first, then Doxorubicin with Enalapril
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: Doxorubicin with Enalapril first, then Doxorubicin alone
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




Primary Outcome Measures :
  1. Number of Patients With Doxorubicin Plasma Concentrations Demonstrating a Significant Increase or Decrease When Doxorubicin Was Given With Enalapril as Compared to When Doxorubicin Was Given Without Enalapril. [ Time Frame: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin ]
    Doxorubicin plasma concentration (DPC) is the primary pharmacokinetic (PK) measure of the exposure. Each patient will have serial PKs performed twice - once with enalapril and once without enalapril. A mean increase or decrease of more than 115 ng/ml in DPC will be considered significant.


Secondary Outcome Measures :
  1. The Number of Participants With a Significant Increase or Decrease in the Baseline Levels of Btype Natriuretic Peptide, Cardiac Troponins, and Urine Microalbumin With or Without Enalapril [ Time Frame: Baseline, 4, 24 and 48 hours after infusion of doxorubicin ]
    Doxorubicin can induce changes in troponin, b-type natriuretic peptide and urine microalbumin. This analysis will determine whether enalapril prevents any of these changes. Statistical significance defined as a p < 0.05.

  2. The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril [ Time Frame: Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin ]
    Doxorubicin is metabolized to doxorubicinol. The effects of enalapril on doxorubicinol will be assessed. Statistical significance defined as a p < 0.05.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00895414


Locations
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United States, Minnesota
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
University of Minnesota Children's Hospital - Fairview
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Anne H. Blaes, MD Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00895414     History of Changes
Other Study ID Numbers: 2008NTLS060
0806M34981 ( Other Identifier: IRB, University of Minnesota )
First Posted: May 8, 2009    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019
Last Verified: May 2019
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:
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Doxorubicin
Liposomal doxorubicin
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Enalapril
Enalaprilat
Maleic acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Antihypertensive Agents