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Trial registered on ANZCTR


Registration number
ACTRN12622000129785
Ethics application status
Approved
Date submitted
8/12/2021
Date registered
27/01/2022
Date last updated
28/01/2024
Date data sharing statement initially provided
27/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II, double blind, placebo controlled, parallel arm, fixed dose, multi-site study to evaluate the safety, feasibility and desirability of conducting a fully powered phase III study of anamorelin for anorexia in people with small cell lung cancer
Scientific title
Phase II, double blind, placebo controlled, parallel arm, fixed dose, multi-site study to evaluate the safety, feasibility and desirability of conducting a fully powered phase III study of anamorelin for anorexia in people with small cell lung cancer
Secondary ID [1] 305601 0
None
Universal Trial Number (UTN)
Trial acronym
LUANA Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anorexia 324031 0
Small cell lung cancer 324770 0
Condition category
Condition code
Cancer 321536 321536 0 0
Lung - Small cell
Diet and Nutrition 322219 322219 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1 / intervention arm. Participants with Small Cell Lung Cancer (SCLC) and anorexia will receive anamorelin HCl 100mg as a tablet.
All participants will be randomised to receive once daily oral dosing of either anamorelin or pacebo (at least 1 hour before first meal of the day) for at least 12 weeks. Treatment (Day 1) will initiate as soon as practicable; ideally prior to cycle 1 of chemotherapy and no later than one day prior to scheduled date of cycle 2 of planned chemotherapy. If chemotherapy is not planned, Day 1 should occur within three weeks of screening visit. At the end of the 12 weeks, participants are invited to enrol in an extension phase where they will continue to receive blinded intervention medication for another 12 weeks. The optional extension (weeks 13-24) is entirely based on participant preference. All participants will receive standard physical activity and diet advice leaflets at baseline from the study nurse as part of a multi-modal intervention. All participants will receive the same information delivered in the same way. Compliance will be assessed at visits at weeks 4, 8 and 12 (plus 18 and 24 for those in the extension phase) using participant record of self-administration (i.e. participant diary) OR counting of the remaining tablets at treatment cessation, if the information has not been recorded in the participant diary.
Intervention code [1] 322002 0
Treatment: Drugs
Comparator / control treatment
Group 2 / control arm or placebo. Participants with SCLC and anorexia will receive matched anamorelin placebo, being a white tablet matched in size and shape to the active intervention. The placebo will contain, Microcrystalline cellulose, 272.65mg; Lactose monohydrate, 272.65mg; Magnesium stearate, 2.7mg; Opadry ® II Yellow 85F42233, 18.4mg.

All participants will be randomised to receive once daily oral dosing of either anamorelin or pacebo (at least 1 hour before first meal of the day) for at least 12 weeks. Treatment (Day 1) will initiate as soon as practicable; ideally prior to cycle 1 of chemotherapy and no later than one day prior to scheduled date of cycle 2 of planned chemotherapy. If chemotherapy is not planned, Day 1 should occur within three weeks of screening visit. At the end of the 12 weeks, participants are invited to enrol in an extension phase where they will continue to receive blinded intervention medication for another 12 weeks. The optional extension (weeks 13-24) is entirely based on participant preference. All participants will receive standard physical activity and diet advice leaflets at baseline from the study nurse as part of a multi-modal intervention. All participants will receive the same information delivered in the same way. Compliance will be assessed at visits at weeks 4, 8 and 12 (plus 18 and 24 for those in the extension phase) using participant record of self-administration (i.e. participant diary) OR counting of the remaining tablets at treatment cessation, if the information has not been recorded in the participant diary.
Control group
Placebo

Outcomes
Primary outcome [1] 329301 0
Feasibility - Recruitment rate determined by review of the screening and withdrawal logs.
Timepoint [1] 329301 0
After 50 participants have been recruited.
Primary outcome [2] 329302 0
Desirability - sufficient signal in efficacy evaluation to suggest phase 3 study would deliver clinically meaningful difference between groups using analysis of primary outcome data
Timepoint [2] 329302 0
After 50 participants have been recruited.
Primary outcome [3] 329303 0
Efficacy - Change in FAACT scores between baseline and week 12 by examination of the data entered,
Timepoint [3] 329303 0
After 50 participants have been recruited,
Secondary outcome [1] 402058 0
Change in body weight recorded in the study worksheets using digital scales provided by the sponsor to each site.
Timepoint [1] 402058 0
Measured at baseline and at weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase)
Secondary outcome [2] 402059 0
Change in lean body mass measured by change in dual x-ray absorptiometry (DEXA) and Bioelectrical Impedance Analysis – BIA
Timepoint [2] 402059 0
Measured at baseline and week 12 post-intervention commencement (plus week 24 for those in the extension phase)
Secondary outcome [3] 402060 0
Change in muscle mass at thoracic (T4) level, measured by electronically stored data from computed tomography (CT) scans
Timepoint [3] 402060 0
This measure will be recorded whenever they are done clinically post-intervention commencement from weeks 4-14 (plus week 24 for those in the extension phase).
Secondary outcome [4] 402061 0
Functional status using clinician-rated Australia-modified Karnofsky Performance Scale (AKPS)
Timepoint [4] 402061 0
Measured as area under the curve from data collected at baseline and at weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase)
Secondary outcome [5] 402062 0
Timed up and go test (TUG) as recorded in study worksheets
Timepoint [5] 402062 0
Measured at baseline and at weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase)
Secondary outcome [6] 402063 0
Dynamic function as measured by a pedometer app or a wearable digital pedometer, for participants who do not have mobiles.
Timepoint [6] 402063 0
Two days prior to visits at weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase)
Secondary outcome [7] 402064 0
Nutritional intake measured by self-reported 3-day food diary, including 2 weekdays and one weekend day prior to visits.
Timepoint [7] 402064 0
At weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase). If participants do not complete the 3-day food diary prior to visits, a 24-h diet recall will be collected by the study nurse at the time of visit.
Secondary outcome [8] 402065 0
Biochemical changes (including IL-6, CRP, albumin and pre-albumin).
Timepoint [8] 402065 0
Baseline and weeks 4, 12 post intervention commencement (and 24 for those in the extension phase).
Secondary outcome [9] 402066 0
Survival measured with record of date of death (overall and cancer specific)
Timepoint [9] 402066 0
From the time of enrolment to date of last data collection (last patient last visit).
Secondary outcome [10] 402067 0
Changes in the Global Impression of Change (GIC)
Timepoint [10] 402067 0
From baseline and weeks 8 and 12 post intervention commencement (and 24 for those in the extension phase)
Secondary outcome [11] 402068 0
Changes in Quality of life assessed with EQ-5D-5L – EuroQoL five-dimensional instrument, and ICECAP-A – ICEpop CAPability measure for Adults.
Timepoint [11] 402068 0
Baseline and weeks 8 and 12 (and 24 for those in the extension phase).
Secondary outcome [12] 402069 0
Changes in participant-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) domain.
Timepoint [12] 402069 0
Baseline and weeks 8 and 12 (and 24 for those in the extension phase).
Secondary outcome [13] 402070 0
Rates of unplanned hospitalisations and length of stay; with primary reasons using hospital records and a diary by participants.
Timepoint [13] 402070 0
At week 12 post intervention commencement (and 24 for those in the extension phase).
Secondary outcome [14] 402071 0
Episodes of febrile neutropaenia will be collected from participant’s medical record
Timepoint [14] 402071 0
At week 12 post intervention commencement (and 24 for those in the extension phase).
Secondary outcome [15] 402072 0
Adverse events from chemotherapy (nausea, vomiting, anorexia, fatigue) from participant’s medical record and from direct report from the participant.
Timepoint [15] 402072 0
At week 12 post intervention commencement (and 24 for those in the extension phase).
Secondary outcome [16] 402073 0
Safety assessments for adverse events using the National Cancer Institutes Common Terminology Criteria for Adverse Events. (NCI CTC AE).V5.0. All known, possible and unexpected adverse events will be assessed at each contact. The most common drug-related treatment emergent adverse events were diabetes and hyperglycaemia (and is an important consideration in the exclusion criteria). Low grade nausea is also common.
Timepoint [16] 402073 0
Each contact from baseline and weeks 1, 4, 8 and 12 post intervention commencement (plus 18 and 24 for those in the extension phase).
Secondary outcome [17] 404522 0
Changes in the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I)
Timepoint [17] 404522 0
From baseline and weeks 8 and 12 post intervention commencement (and 24)

Eligibility
Key inclusion criteria
18 years of age or more
Documented histologic or cytologic diagnosis of small cell lung cancer (limited – one lung and/or nearby lymph nodes; or extensive disease – extends beyond single lung, and extended to other lymph nodes or other parts of the body)
Newly diagnosed with small cell lung cancer with planned systemic therapy OR first recurrence of disease following successful treatment with a documented disease-free interval of at least 6 months
Less than or equal to 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale
Australia-modified Karnofsky Performance status equal to or greater than 50 at screening
Adequate hepatic function [AST (SGOT) and ALT (SGPT) less than or equal to 5 times ULN]
Adequate renal function (calculated creatinine clearance greater than 20 mL/minute)
Female participants shall be: of non-childbearing potential OR of childbearing potential using reliable contraceptive measures AND having a negative urine pregnancy test within 24 hours prior to first dose of investigational product
English-speaking (or have an interpreter available).
The participant must be willing and able to provide written informed consent, and comply with the protocol tests and procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Women who are pregnant OR breastfeeding
Pathology and causes that may impede food intake, as determined by the Investigator. These causes may include but are not limited to: Grade 3 or 4 oral mucositis; Grade 3 or 4 GI disorders (nausea, vomiting, diarrhea, and constipation); OR mechanical obstructions making the person unable to eat.
Having undergone major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomisation. Potential participants must be recovered from acute effects of surgery prior to screening. Participants should not have a current treatment plan to undergo major surgical procedures during the treatment period.
Currently taking androgenic compounds (including but not limited to testosterone, testosterone-like agents, oxandrolone, megestrol acetate, methylphenidate, corticosteroids), olanzapine, prokinetics (including metoclopramide), dronabinol or medical marijuana (medical cannabis) or any other prescription medication or off-label products intended to increase appetite or treat unintentional weight loss [e.g. melatonin, nabilone, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)] – With the exception when any of these medications are administered (short-term) as part of routine chemotherapy/ radiation therapy standard protocols.
On mirtazapine in the previous four weeks.
Pleural effusion requiring thoracentesis.
Pericardial effusion requiring drainage.
Oedema requiring regular diuretics.
Ascites requiring drainage.
Uncontrolled or significant cardiovascular disease, including but not limited to: history of myocardial infarction within the past 3 months; A-V block of second or third degree (but eligible if currently has a pacemaker – with the exception that BIA will not be performed if the person has a pacemaker, due to minor electrical current); unstable angina; congestive heart failure within the past 3 months, if defined as New York Heart Association (NYHA) class III-IV; any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes); uncontrolled hypertension (blood pressure >160 mmHg systolic and >100 mmHg diastolic); heart rate < 50 beats per minute on pre-entry electrocardiogram and participant is symptomatic.
Taking regular medications that may prolong the PR or QRS interval durations, such as any of the antiarrhythmic medications Class I [fast sodium (Na) channel blockers (e.g. quinidine, disopyramide, procainamide, lidocaine, phenytoin, flecainide, propafenone)].
Unable to swallow oral tablets.
Severe gastrointestinal disease (including oesophagitis, gastritis, malabsorption).
History of a gastrectomy.
Recent history of radiotherapy of oesophagus area.
Diabetes mellitus with secondary organ dysfunction (coronary heart disease, previous stroke, renal insufficiency), or poorly controlled diabetes (patients with glycosylated haemoglobin – HbA1c greater than7% or hyperglycaemia – measured as a fasting blood glucose greater than7mmol/L or a random blood glucose greater than11mmol/L) despite receiving clinic-based diabetes care.
1Diagnosis of anorexia caused by other reasons, as determined by the investigator such as: advanced AIDS; heart failure; uncontrolled thyroid disease.
Receiving strong CYP3A4 inhibitors (including clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, etc.) within 14 days of randomization.
Currently receiving tube feedings or parenteral nutrition (either total or partial).
Current use of excessive alcohol or illicit drugs.
Any condition, including the presence of laboratory abnormalities, which in the Investigator’s opinion, places the potential participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret study data.
Enrolment in a previous study with anamorelin HCl or previous exposure to anamorelin HCl.
Actively receiving a concurrent investigational agent or having received an investigational agent within 28 days of Day 1.
Cognitive impairment (Short Blessed Test (SBT) score greater than or equal to 10).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation schedules will be developed for each site using random number tables, generated at an independent central registry. A Central Randomisation Service will be used to facilitate randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment for each participant will be allocated in a 1:1 ratio. Block randomisation will occur in each stratum at each site in randomly assigned blocks of 4 or 8 and will ensure even allocation to each code. Central randomisation will be stratified by limited versus extensive disease and by baseline score of the 5-item Anorexia Symptom Scale Domain from the 12-item FACCT A/CS (10 or less vs more than 10).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A total of 50 participants with small cell lung cancer will be randomised 1:1 to anamorelin HCl 100 mg or placebo in order to have data at 12 weeks on 40 participants (approximately 20 in each treatment arm). Since this is a feasibility study, it is not required to calculate a fully justified sample size for establishing the efficacy of the intervention. It has been suggested, however, as a feasibility study, a sample size between 24 and 50 is acceptable. The findings from this study will be used to inform the calculation of a sample size for a future larger scale phase III trial.

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
12/10/2022
Actual
17/05/2023
Date of last participant enrolment
Anticipated
31/01/2025
Actual
17/05/2023
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
50
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 20809 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 20810 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 20811 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 20812 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 20813 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 20814 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [7] 20819 0
Caritas Christi Hospice - Kew
Recruitment postcode(s) [1] 35628 0
2139 - Concord
Recruitment postcode(s) [2] 35629 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 35630 0
5042 - Bedford Park
Recruitment postcode(s) [4] 35631 0
2170 - Liverpool
Recruitment postcode(s) [5] 35632 0
2065 - St Leonards
Recruitment postcode(s) [6] 35633 0
3065 - Fitzroy
Recruitment postcode(s) [7] 35644 0
3101 - Kew

Funding & Sponsors
Funding source category [1] 309965 0
Commercial sector/Industry
Name [1] 309965 0
Helsinn Healthcare SA
Country [1] 309965 0
Switzerland
Primary sponsor type
University
Name
University of Technology Sydney
Address
PO Box 123 Broadway NSW 2007 Australia
Country
Australia
Secondary sponsor category [1] 311013 0
None
Name [1] 311013 0
Address [1] 311013 0
Country [1] 311013 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309677 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 309677 0
Ethics committee country [1] 309677 0
Australia
Date submitted for ethics approval [1] 309677 0
01/10/2021
Approval date [1] 309677 0
09/02/2022
Ethics approval number [1] 309677 0
2021/ETH11339

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115006 0
Prof David Currow
Address 115006 0
University of Technology Sydney
PO Box 123, Ultimo, New South Wales, 2007,
Country 115006 0
Australia
Phone 115006 0
+61 2 9514 4862
Fax 115006 0
Email 115006 0
david.currow@uts.edu.au
Contact person for public queries
Name 115007 0
Mariana Sousa
Address 115007 0
University of Technology Sydney
PO Box 123, Ultimo, New South Wales, 2007,
Country 115007 0
Australia
Phone 115007 0
+61 2 9515 5106
Fax 115007 0
Email 115007 0
Mariana.deSouzaeSousa@uts.edu.au
Contact person for scientific queries
Name 115008 0
Mariana Sousa
Address 115008 0
University of Technology Sydney
PO Box 123, Ultimo, New South Wales, 2007,
Country 115008 0
Australia
Phone 115008 0
+61 2 9515 5106
Fax 115008 0
Email 115008 0
Mariana.deSouzaeSousa@uts.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual de-identified data collected during the trial will be available to international regulatory agencies and bona fide researchers, upon request.
When will data be available (start and end dates)?
Data will be available following publication of primary outcomes for a period of 15 years.
Available to whom?
Bona fide researchers and regulatory authorities
Available for what types of analyses?
Meta-analysis and subsidy applications. Aggregated data may be used to inform the next phase of the study
How or where can data be obtained?
Any future use of the study data would be at the discretion of the Sponsor/data custodian. Contact details can be obtained from the University of Technology, IMPACCT, Faculty of Health. itcc@uts.edu.au.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePhase II, double blind, placebo controlled, multi-site study to evaluate the safety, feasibility and desirability of conducting a phase III study of anamorelin for anorexia in people with small cell lung cancer: A study protocol (LUANA trial).2023https://dx.doi.org/10.1371/journal.pone.0285850
N.B. These documents automatically identified may not have been verified by the study sponsor.