Pilot Clinical Trial of Macimorelin To Assess Safety and Efficacy in Patients With Cancer Cachexia

Authors

Megan Herodes
Lindsey J Anderson
Samuel Shober
Ellen A Schur
Solomon A Graf
Nicola Ammer
Ramiro Salas
Marco Marcelli
Jose M Garcia

Publication Date

4-1-2023

Journal

Journal of Cachexia, Sarcopenia and Muscle

DOI

10.1002/jcsm.13191

PMID

36860137

PMCID

PMC10067502

PubMedCentral® Posted Date

3-1-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Male, Middle Aged, Aged, Female, Cachexia, Insulin-Like Growth Factor I, Quality of Life, Pilot Projects, Neoplasms, Body Weight, growth hormone secretagogue, macimorelin, ghrelin receptor agonist, cancer cachexia, appetite

Abstract

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.

METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.

RESULTS: Participants receiving at least one of either macimorelin dose were combined (N = 10; 100% male; median age = 65.50 ± 2.12) and compared with placebo (N = 5; 80% male; median age = 68.00 ± 6.19). Efficacy criteria achieved: body weight (macimorelin N = 2; placebo N = 0; P = 0.92); IGF-1 (macimorelin N = 0; placebo N = 0); QOL by Anderson Symptom Assessment Scale (macimorelin N = 4; placebo N = 1; P = 1.00) or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; macimorelin N = 3; placebo N = 0; P = 0.50). No related serious or non-serious adverse events were reported. In macimorelin recipients, change in FACIT-F was directly associated with change in body weight (r = 0.92, P = 0.001), IGF-1 (r = 0.80, P = 0.01), and caloric intake (r = 0.83, P = 0.005), and inversely associated with change in energy expenditure (r = -0.67, P = 0.05).

CONCLUSIONS: Daily oral macimorelin for 1 week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer-induced reductions in body weight, appetite and QOL in larger studies.