A Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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Multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of anamorelin HCl. Approximately 316 patients with advanced NSCLC with cachexia will be randomized 1:1 to anamorelin HCl 100 mg or placebo, taken orally once daily (QD) for a total of 24 weeks. Patients will be instructed to take the study drug at least 1 hour before their first meal of the day

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Cachexia; Cancer, Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Anamorelin Hydrochloride
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Female or male ≥18 years of age Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) Stage III or IV NSCLC. Stage III patient must have unresectable disease Body mass index < 20 kg/m2 with involuntary weight loss of >2% within 6 months prior to screening Ongoing problems with appetite/eating associated with the underlying cancer, as determined by having score of ≤ 17 points on the 5-item Anorexia Symptom Scale and ≤ 37 points on the 12-item FAACT A/CS Patient receiving or not receiving systemic anti-cancer treatment at the time of screening are eligible to participate. Systemic anti-cancer treatment includes first, second, third treatment line with chemotherapy/radiation therapy, immunotherapy or targeted therapy. Patient not receiving systemic anti-cancer treatment is eligible if: Not planning to receive anti-cancer treatment and/or at least 14 days must be elapsed from the completion of prior treatment at the day of screening, in case underwent previous cycle OR Planning to receive anti-cancer treatment within 14 days from randomization and/or at least 14 days must be elapsed from the completion of prior treatment at the day of screening, in case underwent previous cycle OR Patient on palliative care treatment ECOG performance status 0,1 or 2 at screening AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN Adequate renal function, defined as creatinine ≤2 ULN, or calculated creatinine clearance >30 ml/minute Female patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to first dose of investigational product. Notes: Female patient of non-childbearing potential are defined as being in post-menopausal state since at least 1 year; or having documented surgical sterilization or hysterectomy at least 3 months before study participation. Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence. The patient must be willing and able to comply with the protocol tests and procedures All inclusion criteria will be checked at screening visit (Visit 1). Exclusion Criteria: Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors) Woman who is pregnant or breast-feeding Reversible causes of reduced food intake, as determined by the Investigator. These causes may include but are not limited to: NCI CTCAE Grade 3 or 4 oral mucositis, NCI CTCAE Grade 3 or 4 GI disorders [nausea, vomiting, diarrhea, and constipation], mechanical obstructions making patient unable to eat, or severe depression Patient undergoing major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patient must be well recovered from acute effects of surgery prior to screening. Patient should not have plans to undergo major surgical procedures during the treatment period Patient currently taking androgenic compounds (including but not limited to testosterone, testosterone-like agents, oxandrolone, megestrol acetate, corticosteroids, olanzapine, mirtazapine (however, long-term use of mirtazapine for depression for at least four weeks prior to screening is allowed), dronabinol or marijuana (cannabis) or any other prescription medication or off-label products intended to increase appetite or treat unintentional weight loss Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites Patient with uncontrolled or significant cardiovascular disease, including: History of myocardial infarction within the past 3 months A-V block of second or third degree (may be eligible if currently have a pacemaker) Unstable angina Congestive heart failure within the past 3 months, if defined as 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 >150 mm Hg systolic and >95 mm Hg diastolic) Heart rate < 50 beats per minute on pre-entry electrocardiogram and patient is symptomatic Patient on drugs that may prolong the PR or QRS interval durations, such as any of the antiarrhythmic medications Class I (Fast sodium (Na) channel blockers) Patient unable to readily swallow oral tablets Patient with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption) Patient with history of gastrectomy Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus Patient with cachexia caused by other reasons, as determined by the investigator such as: Severe COPD requiring use of home O2, New York Heart Association (NYHA) class III-IV heart failure AIDS Uncontrolled thyroid disease Patient receiving strong CYP3A4 inhibitors within 14 days of randomization Patient currently receiving tube feedings or parenteral nutrition (either total or partial). Current excessive alcohol or illicit drug use Any condition, including the presence of laboratory abnormalities, which in the Investigator's opinion, places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study Enrollment in a previous study with anamorelin HCl Patient actively receiving a concurrent investigational agent, or having received an investigational agent within 28 days of Day 1 All exclusion criteria will be checked at screening visit (Visit 1).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100mg Anamorelin HCl<br> | Drug: Anamorelin Hydrochloride<br>* 100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo Oral Tablet<br>* Placebo (administered as matching placebo tablets in the fasted condition)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body weight | Mean change in body weight | From baseline until week 12 | 
| 5 item Anorexia Symptom Subscale | Mean change in 5-item Anorexia Symptom Subscale | From baseline until week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body weight | Duration of treatment benefit in weight (≥0). | From baseline until week 12 | 
| body weight | Duration of treatment benefit in weight (≥ to a predefined threshold). | From baseline until week 12 | 
| 5 item Anorexia Symptom Subscale | Duration of treatment benefit in anorexia symptoms (≥0), as measured by the 5-item Anorexia Symptom Subscale. | From baseline until week 12 | 
| 5 item Anorexia Symptom Subscale | Duration of treatment benefit in 5-item Anorexia Symptom Subscale (≥ to a predefined threshold). | From baseline until week 12 | 
| FAACT 12-item A/CS domain | Mean change in FAACT 12-item A/CS domain. | From baseline until week 12 | 
| FACIT-F | Mean change in FACIT-F. | From baseline until week 12 | 
| FAACT total score | Mean change in FAACT total score. | From baseline until week 12 |