Enalapril Maleate and Doxorubicin Hydrochloride in Treating Women With Breast Cancer

NCT00895414 | Completed Results DMC

• 2 other identifiers: 2008NTLS0600806M34981
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer

Outcome Measures

Primary Outcomes (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.

  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.

  Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin

Secondary Outcomes (2)

• 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

  Baseline, 4, 24 and 48 hours after infusion of doxorubicin

• The Number of Participants With a Significant Increase or Decrease in Doxorubicin Hydrochloride Metabolite Levels With or Without Enalapril

  Baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion of doxorubicin

Study Arms (2)

Doxorubicin alone first, then Doxorubicin with Enalapril

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; Drug: enalapril maleate

Doxorubicin with Enalapril first, then Doxorubicin alone

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; Drug: enalapril maleate

Interventions

doxorubicin hydrochloride DRUG

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.

Also known as: Adriamycin

Doxorubicin alone first, then Doxorubicin with Enalapril; Doxorubicin with Enalapril first, then Doxorubicin alone

enalapril maleate DRUG

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.

Also known as: Vasotec

Doxorubicin alone first, then Doxorubicin with Enalapril; Doxorubicin with Enalapril first, then Doxorubicin alone

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (2)

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

University of Minnesota Children's Hospital - Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Enalapril; Enalaprilat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Anne Blaes
• Organization: Masonic Cancer Center, University of Minnesota

blaes004@umn.edu

612-626-8138

Study Officials

• Anne H. Blaes, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2009
• First Posted: May 8, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2014
• Study Completion: October 1, 2015
• Last Updated: May 8, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-05

Locations

US (2)