Autophagy Activation for the Alleviation of Cardiomyopathy Symptoms After Anthracycline Treatment, ATACAR Trial

NCT04190433 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 19-007547NCI-2021-13928
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial compares two drug therapy plans for the correction of heart function changes (reduced ejection function) in patients who have undergone anthracycline-based treatment for lymphoma, sarcoma, or breast cancer. "Reduced ejection fraction" means the left ventricle of the heart is pumping a reduced blood volume with each heartbeat. Treatment is recommended, and the purpose of this research is to compare two different drug therapy plans (standard therapy with carvedilol and lisinopril and standard therapy with carvedilol and lisinopril plus pravastatin and spironolactone) and their effects on improvement of heart function. All of these drugs are heart medications, and carvedilol and lisinopril are commonly used to improve heart function. Adding pravastatin, a cholesterol lowering drug with additional beneficial effects on the cardiovascular system, and spironolactone, a water pill with additional beneficial effects on the cardiovascular system, may lead to even better (and faster) improvements in heart function.

Conditions

Breast Carcinoma; Hematopoietic and Lymphoid Cell Neoplasm; Lymphoma; Sarcoma

Outcome Measures

Primary Outcomes (1)

• Delta change in left ventricular ejection fraction [LVEF])

  Will be a comparison of the average delta change in LVEF from start to six months of therapy between group 1 and 2 via an independent groups t-test or Wilcoxon as appropriate after testing distributional assumptions.

  Baseline up to 6 months

Secondary Outcomes (2)

• Cardiac function recovery rates between group 1 and group 2

  Baseline up to 6 months

• Time to recovery of cardiac function between group 1 and group 2

  Baseline up to 6 months

Study Arms (2)

Group I (carvedilol, lisinopril)

ACTIVE COMPARATOR

Patients receive carvedilol orally (PO) and lisinopril orally (PO), up-titrated to maximum tolerated doses as per standard clinical practice for 6 months.

Drug: Carvedilol; Drug: Lisinopril

Group II (pravastatin, spironolactone)

EXPERIMENTAL

Patients receive standard clinical practice therapy as in Group I. Patients also receive pravastatin PO and spironolactone PO for 6 months.

Drug: Carvedilol; Drug: Lisinopril; Drug: Pravastatin; Drug: Spironolactone

Interventions

Carvedilol DRUG

Given PO

Also known as: Coreg

Group I (carvedilol, lisinopril); Group II (pravastatin, spironolactone)

Lisinopril DRUG

Given PO

Also known as: N2-[(1S)-1-Carboxy-3-phenylpropyl]-L-lysyl-L-proline, Dihydrate, Prinivil, Zestril

Group I (carvedilol, lisinopril); Group II (pravastatin, spironolactone)

Pravastatin DRUG

Given PO

Also known as: [1S-[1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha]]-1,2,6,7,8,8a-Hexahydro-beta,!d,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthaleneheptanoic Acid

Group II (pravastatin, spironolactone)

Spironolactone DRUG

Given PO

Also known as: 17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic Acid, gamma Lactone, Acetate, Aldactone, SC 9420, SPL

Group II (pravastatin, spironolactone)

Eligibility Criteria

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

You may qualify if:

• \>= 18 years of age.
• New diagnosis of reduced cardiac function.
• Any prior anthracycline-based cancer therapy for hematological malignancy, breast cancer, or sarcoma.

You may not qualify if:

• History of heart failure (HF) of any class and type, or diagnosis of cardiomyopathy prior to anthracycline therapy.
• On active therapy with a fibrate, niacin or eplerenone, or statin.
• History of myopathy/rhabdomyolysis.
• History of statin intolerance.
• Active treatment for hyperlipidemia.
• History of gout.
• Active treatment for liver disease.
• Unexplained persistent elevations of serum transaminases (above upper limit of normal over two weeks).
• Pregnancy.
• Breast-feeding.
• Hyperkalemia (above upper limit of normal).
• Addison disease.
• Estimated glomerular filtration rate (eGFR) \< 30 mL/minute/1.73 m\^2.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Breast Neoplasms; Hematologic Neoplasms; Lymphoma; Sarcoma

Interventions

Carvedilol; Lisinopril; Pravastatin; Spironolactone; Acetates

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Joerg Herrmann

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 9, 2019
• Study Start: September 1, 2020
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05