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

NCT ID: NCT02416570

Last Updated: 2016-09-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2015-10-31

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.

Conditions

Cachexia; Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Clarithromycin

Clarithromycin 250mg by mouth twice a day for 8 weeks

Group Type: ACTIVE_COMPARATOR

Clarithromycin

Intervention Type: DRUG

Placebo

Placebo matched capsule one capsule by mouth twice a day for 8 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Clarithromycin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roy Castle Lung Cancer Foundation

UNKNOWN

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Wilcock

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Other Identifiers

14102

Identifier Type: -

Identifier Source: org_study_id