LTE1621: Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Heart Failure (PREVENT-HF): A Phase 2B Randomized Placebo-Controlled (Carvedilol) Trial

Categories:

Long-term Effects

Phase I/II

Diseases Treated:

Cancer

Eligibility Overview:

  • Younger than 21 years old at time of cancer diagnosis
  • Weight:
    • Males: more than 55 kilograms (about 121 pounds)
    • Females: more than 50 kilograms (about 110 pounds)
  • Lifetime cumulative anthracycline dose: ≥ 300 mg/m2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy
  • Completed cancer treatment at least 2 years prior to study enrollment
  1. Brief Summary

    Heart failure is one of the leading causes of late morbidity and premature death after successful treatment of childhood cancer with anthracycline chemotherapy. Childhood cancer survivors have a higher risk of heart failure than healthy children; the risk for survivors treated with anthracycline chemotherapy is even greater. Nearly 60 percent of childhood cancer survivors have a history of anthracycline exposure, and almost two-thirds of children exposed to high-dose anthracyclines develop asymptomatic cardiac abnormalities.

    Beta blockers and ACE inhibitors have been successfully used to prevent heart failure in adult non-oncology populations with asymptomatic, left ventricular dysfunction, as well as in certain pediatric non-oncology populations with genetic predisposition to heart failure. This clinical trial will study the effectiveness of carvedilol, a third-generation beta blocker, in reducing the risk of heart failure in childhood cancer survivors who received high dose anthracycline therapy.

    Primary Objective

    • To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of heart failure risk.

    Eligibility Criteria

    Inclusion criteria include:

    • Younger than 21 years old at time of cancer diagnosis
    • Weight:
      • Males: more than 55 kilograms
      • Females: more than 50 kilograms
    • Lifetime cumulative anthracycline dose: ≥ 300 mg/m2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy
    • Completed cancer treatment at least 2 years prior to study enrollment

    Exclusion Criteria include:

    • Current treatment for cardiomyopathy or heart failure
    • Ejection fraction of < 50% by radionuclide angiogram or echocardiogram
    • Shortening fraction of < 25% by echocardiogram
    • History of drug sensitivity or allergic reaction to alpha or beta blockers
    • Low resting systolic blood pressure < 90 mmHg
    • Use of any other blood pressure-lowering medication for hypertension within 30 days of enrollment except calcium channel blockers and diuretics

    Study Design

    Phase II-B randomized double-blind placebo-controlled

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in and outside the U.S.

  2. About this study

    More children are being cured of cancer today, thanks to research and new, better treatments. As these children grow up, however, they may develop complications related to the cancer treatment that they received. Some patients have no complications. Others may develop one or more problems.

    This study will look at childhood cancer survivors who received one type of cancer medicine called anthracycline chemotherapy. Studies have shown that children who received high doses of this type of medicine are more likely to develop heart failure than children who didn’t get the same therapy. Heart failure happens when the heart muscle has been weakened and can’t pump blood as well as it should.

    Researchers in this study want to see if another medicine will lower the risk of heart failure in people who received anthracycline chemotherapy as children. This medicine is called carvedilol. It is a type of medicine known as a beta blocker. Doctors have given this drug to patients for many years to treat heart failure and blood pressure problems. Researchers have also given the drug to children in some studies. In those studies, the researchers found that the medicine lowered the risk of heart failure in some children. Researchers have not studied carvedilol in a large group of childhood cancer survivors who received anthracycline chemotherapy.

    Purpose of this clinical trial

    The main goal of this study is to see if carvedilol will lower the chance of heart failure in childhood cancer survivors who were treated high doses of anthracycline chemotherapy. Researchers want to know the good and bad effects of the medicine in these patients. The study findings may help other childhood cancer survivors in the future by lowering their risk of heart failure.

    Eligibility overview

    • Younger than 21 years old at time of cancer diagnosis
    • Weight:
      • Males: more than 55 kilograms (about 121 pounds)
      • Females: more than 50 kilograms (about 110 pounds)
    • Lifetime cumulative anthracycline dose: ≥ 300 mg/m2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy
    • Completed cancer treatment at least two years prior to study enrollment
  3. LTE1621 Quick View
    Sponsors City of Hope Medical Center
    ClinicalTrials.gov identifier NCT01347970
    Trial start date May 2012
    Estimated enrollment 250 (Up to 50 at St. Jude)
    Study type Interventional
    Study phase Phase II-B
    Conditions Childhood cancer survivor
    Ages All
    Principal investigator Melissa Hudson, MD
    Study sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss LTE1621 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Melissa Hudson, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

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