E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cancer Cachexia in Non-small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064015 |
E.1.2 | Term | Cancer cachexia |
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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 explore the effects on body weight, muscle strength and body composition parameters including body cell mass (BCM) and lean body mass (LBM).
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E.2.2 | Secondary objectives of the trial |
- To explore the effects on health status/Quality of Life (QoL) - To explore the effects on appetite - To evaluate the safety and tolerability of oral imidapril
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have measurable NSCLC disease that has been histologically or cytologically proven and has been recently (≤ 18 months) diagnosed. 2. Male or female patients ≥18 and ≤ 75 years of age. 3. Patients with a history of unintentional and undesired weight loss within 6 months of the screening visit. 4. BMI ≤ 27. 5. Male and female patients must be using effective contraception if the risk of conception exists. 6. Patients who during the 6-week flexible placebo run-in period have a documented weight loss of: - ≥ 1 kg in any 2 weeks, or - ≥ 1.5 kg in 4 weeks, or - ≥ 1.75 kg in 6 weeks. 7. Patients who a) are not expected to undergo chemotherapy during the study or b) have already started a course of cycle/s of chemotherapy before the screening visit, where chemotherapy is defined as any anti tumour medication. 8. Patients with a life expectancy of ≥ 6 months. 9. Patients with Karnofsky Performance score of ≥ 60. 10. Patients (or legal representative) who provide signed written informed consent. |
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E.4 | Principal exclusion criteria |
1. Patients planning to commence chemotherapy (i.e. a course of treatment not prescribed prior to screening) after the screening visit. 2. Patients receiving or planning to receive cranial radiotherapy after the screening visit. 3. Patients with untreated thyrotoxicosis. 4. Patients with a pacemaker or other internal electrical medical device. 5. Patients receiving parenteral nutrition or enteral hyperalimentation. 6. Patients diagnosed with a Diagnostic and Statistical Manual-classified eating disorder such as anorexia nervosa or bulimia. 7. Patients at the screening or baseline visits with: - low blood pressure defined as a sitting systolic blood pressure < 100 mmHg - hypotension defined as grade 2 or greater according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE; formerly known as the National Cancer Institute Common Toxicity Criteria [NCI-CTC]), version 3.0 - clinical symptoms of postural hypotension or orthostatic changes in blood pressure, defined as a decrease in systolic blood pressure of > 20 mmHg or decrease in diastolic blood pressure of > 10 mmHg after shifting from a supine to sitting (with legs dependent) position. 8. Patients at the screening visit with a history of angioneurotic oedema 9. Patients with an active infection. 10. Patients with ascites or generalised oedema, requiring treatment. 11. Patients with renal disease (serum creatinine of > 2 mg/dL); or severe hepatic dysfunction (i.e., aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], or bilirubin levels at toxicity grade 3 or 4 [according to the NCI CTCAE criteria, version 3.0]) at the screening visit. 12. Patients at the screening visit with hyperkalaemia, defined as grade 3 or 4 according to the NCI CTCAE criteria, version 3.0 (> 6.0 mmol/L). 13. Patients at the screening visit with neutrophil counts of < 1500/µL. 14. Patients who are concomitantly receiving any of the following: - potassium-sparing diruetics - lithium - an anabolic regimen (including oxandralone, testosterone, or growth hormone) - oestrogen and progestational agents (e.g. Megastrol), unless being taken for contraception purposes - cyproheptadine hydrochloride, pentoxifylline, thalidomide, dronabinol (Marinol) - angiotensin II antagonist or ACE inhibitor, including imidapril - systemic steroids (other than for the treatment of chemotherapy induced nausea), or have been treated with systemic steroids for more than 21 consecutive days within the previous 3 months prior to the screening visit. [Low dose systemic steroids (equivalent to no more than 10mg prednisolone), given for a period of at least a month prior to screening, are permitted provided that their administration is stable and there is no anticipated change in use during the course of the study]. 15. Patients who were treated with any investigational drug within 30 days or within five plasma half-lives (whichever is the longer) prior to screening visit. 16. Patients on any other clinical trial. 17. Patients who have known hypersensitivity to ACE inhibitors. 18. Patients who are not capable of fully understanding the study requirements or are unwilling/unable to comply with the study procedures. 19. Patients with malignancy (unless in remission) other than NSCLC. 20. Pregnant or lactating female patients. 21. Patients with a medical condition that, in the opinion of the investigator, would compromise their ability to participate in the study. 22. History of known alcohol or drug abuse. 23. Patients who have <80% compliance during the placebo run-in phase with regards to taking their study medication.
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E.5 End points |
E.5.1 | Primary end point(s) |
- the rate of change and percentage change in BCM from randomisation to the end of study treatment, measured using the Quantum/STA bioimpedance analyser
- the rate of change and percentage change of LBM from randomisation to the end of study treatment, measured by bioimpedance
- the rate of change and percentage change in body weight using Tanita scales from randomisation to end of treatment
- the rate of change and percentage change in muscle strength (determined by hand-grip dynamometry measurements) from randomisation to the end of study treatment
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Placebo (single-blind) run-in phase: 2 to 6 weeks duration at the start of trial |
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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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 1 |
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 | 1 |
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 |