E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unintentional weight loss , cachexia, increases chemotherapy toxicity and reduces survival and quality of life. There is no treatment available today. Based on knowledge of cachexia pathophysiology and previous single intervention studies, we now investigate in a RCT trial if multimodal cachexia intervention(nutritional therapy with EPA, physical exercise and anti-inflammatory treatment(ibuprofen))+standard treatment improves weight and physical performance better than standard treatment alone. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with advanced cancer and cachexia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
Body weight – difference between intervention and control group at study endpoint (T2) |
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E.2.2 | Secondary objectives of the trial |
All endpoints will be assessed at T2 between the two groups Muscle Mass: difference using CT L3 technique Physical activity: difference in step count assessed by ActivPAL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of lung cancer or pancreatic cancer where the diagnosis is based on histological, radiological or multidisciplinary team (MDT) evaluation 2. Patients with non-small cell lung cancer (stage III or IV) or pancreatic adenocarcinoma (stage III or IV) due to commence first or second line anticancer treatment (defined as chemotherapy or chemo-radiotherapy or targeted therapy 3. Have a staging CT within 4 weeks of commencement of anti-cancer therapy (in patients where staging CT is out-with this period, further CT scanning will be undertaken. PET-CT’s are also appropriate) 4. Have completed all other baseline assessments within one week prior to first course of anti-cancer treatment 5. Provide written informed consent 6. Able to comply with trial interventions (in the opinion of referring clinician) e.g. willing and able to do light exercise and take ONS as well as no major contraindications against ibuprofen*. 7. Karnofsky Performance Status ≥70 8. ≥ 18 years of age 9. Femal patients of childbearing potential must have a negative pregnancy test performed during screening period.
*The use of proton-pump inhibitor should be decided upon by the physician in charge of the patient if the patient has a history of dyspepsia or gastric ulcer. If the patient has had a recent gastric ulcer the patient is not eligible as she/he has a major contraindication to ibuprofen |
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E.4 | Principal exclusion criteria |
1. Neuro-endocrine pancreatic cancer 2. Creatinine clearance <30ml/min.** 3. Receiving parenteral nutrition or enteral nutrition via feeding tube 4. Patients receiving neo-adjuvant anti-cancer therapy 5. BMI >30 kg/m2 6. Use of appetite stimulants or anabolic/anti-catabolic agents (such as megestrol acetate, progestational agents, marijuana growth hormone, dronabinol, or other anabolic agent) within 30 days prior to study baseline 7. Concomitant steroid (>10mg/d prednisolone or equivalent) treatment for less than three months prior to inclusion (inhaled, optical or pulsed oral steroids (up to 10 days use) are permitted) 8. Concomitant long term (>1 week) NSAID or Aspirin treatment*** 9. 9. Women during pregnancy, breast-feeding or women of child bearing potential , who are not using or not willing to use highly effective methods of contraception**** for the entire study duration unless they are surgically sterilized / hysterectomized. 10. Concomitant anti-coagulant treatment (e.g. warfarin or heparin) 11. Hypersensitivity to Ibuprofen or any of the constituents in Ibuprofen tablets 12. Patients who have previously shown hypersensitivity reaction (e.g. asthma, rhinitis, angioedema or urticarial) in response to aspirin or other non-steroidal anti-inflammatory drugs 13. Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) 14. History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy 15. Patients with conditions involving an increased tendency to bleeding 16. Severe hepatic failure, renal failure or severe heart failure (NYHA Class IV) 17. Patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
** Patients who are receiving pemetrexed and have mild to moderate renal insufficiency (Creatinine Clearance 45-79 ml/min) should not take ibuprofen for 2 days before, on the day of and 2 days after pemetrexed administration.
*** Patients who are taking aspirin, NSAID or Cox 2 inhibitors prior to study entry can participate in the study providing these medications are either permanently or temporarily stopped during trial participation. This should only be done following discussion with the clinician responsible for the patient’s general care – usually general practitioner or family physician. In patients who are taking other medication which may interact with ibuprofen, e.g. fluconazole, the risks/benefits of these medications should be considered and discussed with the study physician, prior to patient recruitment. **** Highly effective contraceptive methods (Pearl Index <1) are: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable • intrauterine device • intrauterine hormone-releasing system • vasectomized partner • sexual abstinence
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E.5 End points |
E.5.1 | Primary end point(s) |
Body weight will be used as the primary end point in the MENAC trial. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (T0), Midpoint week 3 (T1), Endpoint week 6 (T2) |
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E.5.2 | Secondary end point(s) |
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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 | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Patients in the control group receive standard care |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patients in the control group receive standard care |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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For the purposes of Clinical Trial Authorization the trial is deemed to have ended 30 days after follow-up however date of death will be recorded where applicable. The trial will continue for 3 months after the last patient has completed to ensure censoring is kept to a minimum. For the purposes of the ethics, the study end date is deemed to be the date of the last data capture. The sponsor can also terminate the study for safety reasons. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |