Cachexia, Lung Cancer
Conditions
Keywords
Clarithromycin
Brief summary
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
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.
Interventions
DRUGClarithromycin
DRUGPlacebo
Sponsors
Roy Castle Lung Cancer Foundation
University of Nottingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of a phase 3 study | 1 year | The number of patients recruited to the study as a measure of feasibility. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of clarithromycin | 1 year | Number of patients taking \>80% of prescribed doses as a measure of tolerability. |
| Safety of clarithromycin | 1 year | Number of adverse events as a measure of safety. |
| Effect of clarithromycin | 1 year | Change from baseline in body composition at 8 weeks as a measure of effect. |
Outcome results
None listed