Is Clarithromycin a Potential Treatment for Cachexia in People With Lung Cancer?

This study aims to identify if clarithromycin (CLM) has potential as a widely available and inexpensive treatment for cachexia (the loss of muscle mass) in people with non-small cell lung cancer (NSCLC). Half the participants will receive clarithromycin and half will receive a placebo.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Cachexia
• Intervention / Treatment: Drug: Placebo; Drug: Clarithromycin

Detailed Description

Clarithromycin has been reported to significantly improve markers of inflammation, body weight, need for hospital admission and survival in 42 patients with NSCLC. Compared to patients receiving best supportive care only, those receiving Clarithromycin had an improved median survival of ~8 months (535 vs. 277 days), stayed at home longer (439 vs. 139 days) and reported no adverse effects.

In another study, 33 patients with NSCLC were given Clarithromycin for 3 months and compared to a matched control group there was a reduction in IL-6 levels which correlated with an improvement in body weight (gain 4 vs. 1kg) and survival. Thus, by reducing inflammation, Clarithromycin may be impeding the cachectic process, preserving body weight, physical function and independence and increasing survival.

These studies of Clarithromycin in NSCLC have limitations, e.g. lack of placebo-control, no direct assessment of lean body mass.

This feasibility study will obtain data to inform the viability and design of a larger randomised, double-blind, placebo-controlled, phase III study.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults with stage IV, pathologically confirmed, NSCLC not suitable for/declining/not tolerating 1st/2nd-line palliative chemotherapy, or following completion of 1st/2nd-line palliative chemotherapy
• A likely prognosis of ≥3 months.
• Cachexia on the basis of any of the following, weight loss >5% over past 6 months, or BMI <20kg/m2 and weight loss >2%, or appendicular skeletal muscle index determined by duel energy x-ray absorptiometry consistent with sarcopenia and weight loss >2%.
• Systemic inflammation on the basis of a C-reactive protein >10mg/L.
• Adequate renal function as defined by creatinine ≤132micromol/L and eGFR ≥30mL/min/1.73m2
• Adequate liver function as defined by the following parameters, bilirubin ≤25micromol/L, and AST and ALT ≤2 times upper limit of normal, unless liver metastases, in which case ≤5 times upper limit of normal
• Prepared to suspend, if necessary, the use of certain statins and/or substitute the use of domperidone for an alternative anti-emetic for the duration of the study

Exclusion Criteria:

• ECOG Performance Status 3 or 4
• Little or no food intake
• Weight loss >10% in 1 month or >20% in total
• Known hypersensitivity to clarithromycin
• Inability to accurately measure QT interval, e.g. atrial fibrillation
• QTc prolongation >450 milliseconds in a male, or 470 milliseconds in a female
• History of ventricular arrhythmia
• Severe cardiac insufficiency (NYHA class >2)
• Untreated hypokalaemia/hypomagnesaemia
• Active infection requiring antibiotics
• Current or recent (within last 4 weeks) history of Clostridium difficile, eating disorder, dysphagia, malabsorption or diarrhoea
• Untreated adrenal or thyroid diseases
• Brain metastases
• Use of corticosteroids/progestogens
• Use of chemotherapy, other immunosuppressive, or antiviral (e.g. hepatitis C, HIV) drugs within 4 weeks
• Drugs which are contra-indicated (except certain statins which can be temporarily suspended and domperidone which can be substituted for an alternative anti-emetic) or should be avoided in patients receiving clarithromycin, either because of the risk of a drug-drug interaction and/or prolonged QT
• Pregnancy
• Breast Feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clarithromycin; Clarithromycin 250mg by mouth twice a day for 8 weeks	Drug: Clarithromycin
Placebo Comparator: Placebo; Placebo matched capsule one capsule by mouth twice a day for 8 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of a phase 3 study	The number of patients recruited to the study as a measure of feasibility.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of clarithromycin	Number of patients taking >80% of prescribed doses as a measure of tolerability.	1 year
Safety of clarithromycin	Number of adverse events as a measure of safety.	1 year
Safety of clarithromycin	Number of patients with prolongation of the QT interval as a measure of safety.	1 year
Effect of clarithromycin	Change from baseline in body composition at 8 weeks as a measure of effect.	1 year
Effect of clarithromycin	Change from baseline in hand grip strength at 8 weeks as a measure of effect.	1 year
Effect of clarithromycin	Change from baseline in 5 repetition sit to stand test speed at 8 weeks as a measure of effect.	1 year
Effect of clarithromycin	Change from baseline in 4 metre gait speed at 8 weeks as a measure of effect.	1 year
Effect of clarithromycin	Change from baseline in EQ-5D-5L at 8 weeks as a measure of effect.	1 year
Effect of clarithromycin	Change from baseline in QLC Q30 at 8 weeks as a measure of effect.	1 year

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Roy Castle Lung Cancer Foundation
• Investigators: Principal Investigator: Andrew Wilcock, University of Nottingham

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: March 6, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 15, 2015

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Clarithromycin
• Additional Relevant MeSH Terms: Metabolic Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Nutrition Disorders; Body Weight; Respiratory Tract Neoplasms; Thoracic Neoplasms; Body Weight Changes; Emaciation; Weight Loss; Lung Neoplasms; Wasting Syndrome; Cachexia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin
• Other Study ID Numbers: 14102