Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol

Our plain-English summary of Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol, by S.N. Hoon, K. Fyfe, C.J. Peddle-McIntyre, et al (BMJ Open Respiratory Research, 2020).

The study

• Authors: S.N. Hoon, K. Fyfe, C.J. Peddle-McIntyre, S. Bowyer, F. Hawkins, E. Jeffery, H.J. Chih, J. Creaney, A. Nowak, F. Brims
• Journal: BMJ Open Respiratory Research
• Published: 2020;7(1)
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia.

Methods And Analysis: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5% weight loss in 6 months or body mass index <20 kg/m2 with weight loss >2%).

Ethics And Dissemination: Ethical approval has been granted. Results will be reported in peer-reviewed publications.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This article is a protocol. It describes a planned trial, called ANTHEM, and reports no results. The authors planned a single-centre, randomised, double-blind, placebo-controlled phase II cross-over pilot study at Sir Charles Gairdner Hospital in Perth, Western Australia, with recruitment due to open in early 2020. The trial was to enrol 40 adults with malignant pleural mesothelioma and cachexia, defined as more than 5% weight loss in 6 months, or a body mass index under 20 kg/m2 with weight loss over 2%. Patients with peritoneal disease were to be excluded. Each participant was to take the drug anamorelin, 100 mg once daily, for 28 days and a placebo for 28 days, in random order, with a 3-day washout between them. The main outcome was the change in arm and leg muscle mass relative to height, measured by DXA scan, at the end of the first period. The study examined a drug, not asbestos exposure. The authors noted that larger trials would be needed to test effects on survival.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Protocol (no results) for a single-centre, randomised, double-blind, placebo-controlled phase II modified cross-over pilot trial. Two 28-day treatment periods were separated by a 3-day washout. The primary outcome was change in appendicular skeletal muscle mass relative to height, measured by DXA scan, at the end of period 1.
• Who was studied: 40 adults were planned, with histologically or cytologically confirmed malignant pleural mesothelioma and cachexia (more than 5% weight loss in 6 months, or body mass index under 20 kg/m2 with weight loss over 2%), performance status 0 to 2, and life expectancy over 3 months. Patients with peritoneal disease were excluded. Recruitment was to be through Sir Charles Gairdner Hospital, Perth, Western Australia, opening in early 2020.
• Exposure: The study examined a drug, not asbestos. Participants were to take anamorelin 100 mg oral tablet once daily in one 28-day period and placebo in the other, in random order.
• The authors' conclusion: The authors concluded that anorexia is a major symptom in malignant pleural mesothelioma, that weight loss and cachexia are common and have prognostic importance, and that better management of anorexia may improve quality of life and appendicular skeletal muscle mass. They stated that larger clinical trials will be needed to test the effects of anamorelin on survival, treatment toxicities and adherence.
• Limitations the authors state:
  • The authors noted the expected dropout and relatively small sample size, and planned an adaptive-recruitment design to replace early withdrawals.
  • Outcome assessors were to be blinded, but there was to be no independent review of assessments.
  • The authors considered possible carry-over bias on muscle mass from period 1 to period 2. For that reason the primary outcome compares groups only at the end of period 1.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Cachexia, Malignant Mesothelioma, Quality of Life, Clinical Trial.

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