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

University of Nottingham

Status and phase

Terminated

Phase 2

Conditions

Lung Cancer

Cachexia

Treatments

Drug: Clarithromycin

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02416570

14102

Details and patient eligibility

About

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.

Full 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.

Enrollment

1 patient

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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