search
Back to results

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

Primary Purpose

Cachexia, Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Clarithromycin
Placebo
Sponsored by
University of Nottingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cachexia focused on measuring Clarithromycin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Clarithromycin

    Placebo

    Arm Description

    Clarithromycin 250mg by mouth twice a day for 8 weeks

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

    Outcomes

    Primary Outcome Measures

    Feasibility of a phase 3 study
    The number of patients recruited to the study as a measure of feasibility.

    Secondary Outcome Measures

    Tolerability of clarithromycin
    Number of patients taking >80% of prescribed doses as a measure of tolerability.
    Safety of clarithromycin
    Number of adverse events as a measure of safety.
    Safety of clarithromycin
    Number of patients with prolongation of the QT interval as a measure of safety.
    Effect of clarithromycin
    Change from baseline in body composition at 8 weeks as a measure of effect.
    Effect of clarithromycin
    Change from baseline in hand grip strength at 8 weeks as a measure of effect.
    Effect of clarithromycin
    Change from baseline in 5 repetition sit to stand test speed at 8 weeks as a measure of effect.
    Effect of clarithromycin
    Change from baseline in 4 metre gait speed at 8 weeks as a measure of effect.
    Effect of clarithromycin
    Change from baseline in EQ-5D-5L at 8 weeks as a measure of effect.
    Effect of clarithromycin
    Change from baseline in QLC Q30 at 8 weeks as a measure of effect.

    Full Information

    First Posted
    March 6, 2015
    Last Updated
    September 15, 2016
    Sponsor
    University of Nottingham
    Collaborators
    Roy Castle Lung Cancer Foundation
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02416570
    Brief Title
    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

    2. Study Status

    Record Verification Date
    September 2016
    Overall Recruitment Status
    Terminated
    Why Stopped
    At 6 months 1 participant recruited. Study deemed not feasible and discontinued.
    Study Start Date
    April 2015 (undefined)
    Primary Completion Date
    October 2015 (Actual)
    Study Completion Date
    October 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Nottingham
    Collaborators
    Roy Castle Lung Cancer Foundation

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cachexia, Lung Cancer
    Keywords
    Clarithromycin

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    1 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Clarithromycin
    Arm Type
    Active Comparator
    Arm Description
    Clarithromycin 250mg by mouth twice a day for 8 weeks
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo matched capsule one capsule by mouth twice a day for 8 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Clarithromycin
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Primary Outcome Measure Information:
    Title
    Feasibility of a phase 3 study
    Description
    The number of patients recruited to the study as a measure of feasibility.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Tolerability of clarithromycin
    Description
    Number of patients taking >80% of prescribed doses as a measure of tolerability.
    Time Frame
    1 year
    Title
    Safety of clarithromycin
    Description
    Number of adverse events as a measure of safety.
    Time Frame
    1 year
    Title
    Safety of clarithromycin
    Description
    Number of patients with prolongation of the QT interval as a measure of safety.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in body composition at 8 weeks as a measure of effect.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in hand grip strength at 8 weeks as a measure of effect.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in 5 repetition sit to stand test speed at 8 weeks as a measure of effect.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in 4 metre gait speed at 8 weeks as a measure of effect.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in EQ-5D-5L at 8 weeks as a measure of effect.
    Time Frame
    1 year
    Title
    Effect of clarithromycin
    Description
    Change from baseline in QLC Q30 at 8 weeks as a measure of effect.
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Andrew Wilcock
    Organizational Affiliation
    University of Nottingham
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs