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
University of Technology Sydney
50 participants
May 17, 2023
Interventional
Conditions
Summary
Loss of appetite, known as anorexia, is a distressing symptom for people with cancer resulting in considerable involuntary weight loss, reduced physical activity, poor prognosis and death. To date, there are limited treatment options and no registered therapy for the treatment of cancer anorexia. Patients with small cell lung cancer have high prevalence of weight loss. The aim of this study is to determine whether it is feasible and desirable to conduct a study of anamorelin for the treatment of anorexia symptoms in patients with small cell lung cancer. – Who is it for? You may be eligible for this study if you are aged 18 years or older, have been diagnosed with small cell lung cancer (local or advanced) and have planned systemic therapy OR have first recurrence of disease after at least 6 months of documented disease-free following successful treatment, and you are at risk of developing anorexia based on a dietary score. Study details Participants who choose to enrol in this study will be randomly allocated (by chance, similar to flipping a coin) to receive 12 weeks of either anamorelin or placebo as an oral tablet. Participants will be assessed [~4 weekly] by the study team for the duration of treatment to monitor safety, feasibility and acceptability of study procedures and medication, and suitability of outcome measures for a full trial. Participants will be asked to undergo some laboratory tests and scans and to complete a study diary and a number of questionnaires at 1, 4, 8 and 12 weeks post-treatment commencement. These will involve answering questions regarding general well-being and quality of life, pain, nausea, side effects, capability in daily functions and dietary intake. Participants will also be asked to monitor their physical activity using a pedometer or mobile app. At the end of the 12 week study, all participants will be invited to continue taking their allocated medication for another 12 weeks, with additional questionnaires and assessments to be undertaken at 18 and 24 weeks after starting the medication. This extension stage is completely optional and up to the participant. It is hoped that this study will help clinicians to evaluate the safety, feasibility and desirability of anamorelin as a treatment for cancer-related anorexia and for a phase III trial.
Eligibility
Inclusion Criteria10
- 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.
Exclusion Criteria24
- 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.
- Diagnosis 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).
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Interventions
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.
Locations(7)
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ACTRN12622000129785