Clinical trial NCT02416570: Is Clarithromycin a Potential Treatment for Cachexia in People With Lung Cancer?
Official title: Is Clarithromycin a Potential Treatment for Cachexia in People With Lung Cancer?
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cachexia
Lung Cancer
Keywords: Clarithromycin
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Roy Castle Lung Cancer Foundation
First posted: 2015-04-15
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of a phase 3 study
timeFrame: 1 year
Secondary outcomes:
measure: Tolerability of clarithromycin
timeFrame: 1 year
measure: Safety of clarithromycin
timeFrame: 1 year
measure: Safety of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
measure: Effect of clarithromycin
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: University of Nottingham
name: Andrew Wilcock
role: PRINCIPAL_INVESTIGATOR
References: