E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of malignancy associated weight loss or anorexia in patients with NSCLC |
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E.1.1.1 | Medical condition in easily understood language |
Weight loss or anorexia in patients with non-small cellular lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate superiority of anamorelin HCl vs placebo on the gain in body weight and improvement in anorexia symptoms |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of anamorelin HCl and to further evaluate anamorelin efficacy profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed written informed consent 2. Female or male ≥18 years of age 3. Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) Stage III or IV NSCLC. Stage III patient must have unresectable disease 4. Body mass index < 20 kg/m2 with involuntary weight loss of >2% within 6 months prior to screening 5. 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 6. 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: a. 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 b. 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 c. Patient on palliative care treatment 7. ECOG performance status 0,1 or 2 at screening 8. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN 9. Adequate renal function, defined as creatinine ≤2 x ULN, or calculated creatinine clearance >30 ml/minute 10. 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 11. The patient must be willing and able to comply with the protocol tests and procedures |
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E.4 | Principal exclusion criteria |
1. Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors) 2. Woman who is pregnant or breast-feeding 3. Reversible causes of reduced food intake, as determined by the Investigator. These causes may include but are not limited to: a. NCI CTCAE Grade 3 or 4 oral mucositis, b. NCI CTCAE Grade 3 or 4 GI disorders [nausea, vomiting, diarrhea, and constipation], c. mechanical obstructions making patient unable to eat, or d. severe depression 4. 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 5. 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 6. Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites 7. Patient with uncontrolled or significant cardiovascular disease, including: a. History of myocardial infarction within the past 3 months b. A-V block of second or third degree (may be eligible if currently have a pacemaker) c. Unstable angina d. Congestive heart failure within the past 3 months, if defined as NYHA class III-IV e. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes) f. Uncontrolled hypertension (blood pressure >150 mm Hg systolic and >95 mm Hg diastolic) g. Heart rate < 50 beats per minute on pre-entry electrocardiogram and patient is symptomatic 8. 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) 9. Patient unable to readily swallow oral tablets 10. Patient with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption) 11. Patient with history of gastrectomy 12. Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus 13. Patient with cachexia caused by other reasons, as determined by the investigator such as: a. Severe COPD requiring use of home O2, b. New York Heart Association (NYHA) class III-IV heart failure c. AIDS d. Uncontrolled thyroid disease 14. Patient receiving strong CYP3A4 inhibitors within 14 days of randomization 15. Patient currently receiving tube feedings or parenteral nutrition (either total or partial). 16. Current excessive alcohol or illicit drug use 17. 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 18. Enrollment in a previous study with anamorelin HCl 19. Patient actively receiving a concurrent investigational agent, or having received an investigational agent within 28 days of Day 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Mean change in body weight from baseline over 12 weeks. •Mean change in 5-item Anorexia Symptom Subscale from baseline over 12 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Duration of treatment benefit in weight (≥0) from baseline over 12 weeks. •Duration of treatment benefit in weight (≥ to a predefined threshold) from baseline over 12 weeks. •Duration of treatment benefit in anorexia symptoms (≥0) from baseline over 12 weeks, as measured by the 5-item Anorexia Symptom Subscale. •Duration of treatment benefit in 5-item Anorexia Symptom Subscale (≥ to a predefined threshold) from baseline over 12 weeks. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
United States |
Poland |
Romania |
Germany |
Belgium |
Croatia |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |