Phase 2
N=182
Carvedilol in Preventing Heart Failure in Childhood Cancer Survivors
Hematopoietic and Lymphoid Cell Neoplasm · Malignant Solid Neoplasm
Bottom Line
View on ClinicalTrials.gov: NCT02717507 ↗Enrolled (actual)
182
Serious AEs
0.0%
Results posted
Sep 2023
Primary outcome: Primary: Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) — -0.1372; -0.0893; -0.2167; 0.3215 z-score — p=0.15
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Carvedilol (Drug); Laboratory Biomarker Analysis (Other); Pharmacogenomic Study (Other); Pharmacological Study (Other); Placebo Administration (Other); Quality-of-Life Assessment (Other); Questionnaire Administration (Other)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Average Left-Ventricular Wall Thickness-Dimension Ratio Z-score (LVWT/Dz) |
-0.1372; -0.0893; -0.2167; 0.3215; -0.2416; -0.2367 | 0.15 |
| SECONDARY Average Left Ventricular End-systolic Wall Stress |
93.2892; 90.6135; 90.3088; 96.8356; 88.984; 96.0616 | 0.03 sig |
| SECONDARY Average Left Ventricular End-systolic Dimension |
03.2765; 3.2396; 3.2901; 3.3023; 3.262; 3.2964 | 0.05 |
| SECONDARY Average Left Ventricular End-systolic Volume |
42.2193; 39.7354; 41.6128; 41.3839; 42.8437; 41.8113 | 0.17 |
| SECONDARY Average Left Ventricular End-diastolic Dimension |
4.5836; 4.5269; 4.6035; 4.565; 4.636; 4.5884 | 0.01 sig |
| SECONDARY Average Left Ventricular End-diastolic Volume |
99.7507; 93.3155; 99.3216; 95.7434; 102.378; 96.5002 | 0.36 |
| SECONDARY Average Left Ventricular Mass |
57.4862; 57.9322; 58.2839; 57.0924; 60.2116; 59.4508 | 0.59 |
| SECONDARY Average Fractional Shortening |
28.5362; 28.4339; 28.5409; 27.6866; 29.6121; 28.1085 | 0.84 |
| SECONDARY Average Ejection Fraction |
57.6; 57.42; 58.16; 56.84; 58.07; 56.61 | 0.49 |
| SECONDARY Average Peak Early Atrial Divided by Peak Late Atrial Velocities |
1.728; 1.732; 1.642; 1.769; 1.723; 1.722 | 0.82 |
| SECONDARY Average N-terminal Pro B-type Natriuretic Peptide |
27.3836; 31.4324; 31.8406; 34.1857; 26.8203; 33.2941 | 0.24 |
| SECONDARY Average Cardiac N-terminal Pro B-type Natriuretic Peptide |
85.6301; 115.7222; 90.7536; 128.9565; 87.7167; 115.6364 | 0.55 |
| SECONDARY Average Cardiac Troponin I |
0.00446; 0.0011; 0.00265; 0.00174; 0.00467; 0.00742 | 0.51 |
| SECONDARY Average Galectin-3 |
4.4464; 5.2538; 4.3252; 4.3735; 3.7345; 4.3415 | 0.92 |
| SECONDARY Proportion of Patients With Reportable Adverse Events as Described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). |
0.0267; 0 | — |
| SECONDARY Average Bilirubin |
0.5634; 0.4989; 0.5973; 0.4942; 0.563; 0.4969 | 0.82 |
| SECONDARY Average Aspartate Aminotransferase |
26.608; 25.773; 24.068; 26.342; 25.426; 27.014 | 0.97 |
| SECONDARY Average Alanine Aminotransferase |
29.122; 30.467; 28.014; 32.158; 30.148; 31.155 | 0.72 |
| SECONDARY Proportion of Participants With Average Adherence > 90% |
0.483; 0.517 | — |
| SECONDARY Proportion of Patients Who Responded "Moderately", "Quite a Bit", or "Extremely" to the Question of How Bothersome the Listed Symptom Was at Any Post-day 0 Assessment Time Point. |
0.0533; 0.1316; 0.0933; 0.0789; 0.1467; 0.1447 | — |
Summary
This phase IIb trial studies how well low-dose carvedilol works in preventing heart failure in cancer survivors exposed to high dose anthracyclines for management of childhood cancer. Patients who received high-dose anthracycline chemotherapy are at a much greater risk for developing heart failure compared to survivors who didn't get any anthracycline chemotherapy. Heart failure happens when the heart muscle has been weakened and can't pump blood as well as it should. Carvedilol may help lower the risk of cardiovascular complications.
Eligibility Criteria
Inclusion Criteria
- Males and females must weigh >= 40 Kg
- Patient must have had a cancer diagnosis = 250 mg/m^2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the anthracycline dose threshold must be met as part of the treatment of a cancer that was diagnosed at = 2 years prior to study enrollment
Exclusion Criteria
- Receiving treatment for cardiomyopathy or heart failure
- Ejection fraction of 3 times upper limit of institutional normal
- Gastrointestinal, or biliary disorders that could impair absorption, metabolism, or excretion of orally administered medications
- Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or hypothyroidism) not controlled with medication
- Uncontrolled diabetes (controlled diabetes per the American Diabetes Association and International Diabetes Center's Glycemic Target Goals is hemoglobin A1C < 7%)
- Anemia (hematocrit < 28%)
- Currently using select CYP2D6 inhibitor or inducer medications
- Inability to swallow pills
- Female patients who are pregnant are not eligible; women of childbearing potential require a negative pregnancy test prior to starting study drug
- Lactating females are not eligible unless they have agreed to not breastfeed their infants
- Sexually active female patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method during study and for 2 months after stopping the study drug; abstinence is an acceptable method of birth control
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Data sourced from ClinicalTrials.gov (NCT02717507). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.