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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cachexia, Lung Cancer

Intervention / Treatment
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* Drug: Clarithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clarithromycin