E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer related Cachexia (NSCLC-C) |
|
E.1.1.1 | Medical condition in easily understood language |
Weight-loss and lean body mass loss due to non-small cell lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064015 |
E.1.2 | Term | Cancer cachexia |
E.1.2 | System Organ Class | 100000004861 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002646 |
E.1.2 | Term | Anorexia |
E.1.2 | System Organ Class | 100000004861 |
|
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 |
1. To evaluate the effect of Anamorelin HCl on lean body mass (LBM) as measured by dual energy X-ray absorptiometry (DXA)
2. To evaluate the effect of Anamorelin HCl on muscle strength as measured by handgrip strength (HGS)
|
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of Anamorelin HCl on body weight
2. To evaluate the effect of Anamorelin HCl on quality of life as assessed using the FAACT (Functional Assessment of Anorexia/Cachexia Treatment) and the FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue)
3. To evaluate the effect of Anamorelin HCl on overall survival
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Cost and cost effectiveness analysis alongside randomized,
double-blind placebo-controlled trials of Anamorelin HCL in the
treatment of non-small cell lung cancer – cachexia (HT-ANAM-301
[ROMANA 1], HT-ANAM-302 [ROMANA 2] and HT-ANAM-303 [ROMANA
3]).
Protocol No.: HE-01 version of 27.09.2012
The proposed economic analysis is to estimate the differences in costs
and health outcomes that are likely to translate into Anamorelin HCI
being a cost-effective way of controlling cachexia. The primary objective
of this economic study is to measure the costs and cost-effectiveness of
Anamorelin HCI from the societal perspective.
The secondary objectives are as follows: To estimate the financial and
economic costs of providing Anamorelin HCI from the country in analysis
perspective; To estimate the cost of cachexia events to the patient and
their caregiver(s); To evaluate the effect of Anamorelin HCI vs. placebo
on medical resource utilisation, including the frequency of outpatient
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and inpatient hospitalisations, concomitant medications and additional
investigations; To obtain utility values from the patients in the ROMANA
studies through the EuroQoL-5 dimension questionnaire (EQ-5D)1 in
order to estimate Quality Adjusted Life Years (QALYs) as an intermediate
effectiveness measure of these trials and; To assess the incremental
costs and cost-effectiveness of Anamorelin HCI compared to placebo
after one year based on survival data. |
|
E.3 | Principal inclusion criteria |
•Females and males at least 18 years of age
•Documented histologic or cytologic diagnosis of AJCC Stage III or IV NSCLC. Stage III patients must have unresectable disease.
•With regard to chemotherapy and/or radiation therapy: Patients may be receiving maintenance chemotherapy (after first line chemotherapy), Patients may be initiating a new chemotherapy (first or second line) and/or radiation therapy regimen within 7 days of study drug randomization, patients are receiving no chemotherapy and/or radiation for NSCLC
•Involuntary weight loss of greater than/equal to 5% body weight within 6 months prior to screening or a screening BMI <20 kg/m2.
•Body mass index less than/equal to 30 kg/m2
•ECOG less than/equal to 2 |
|
E.4 | Principal exclusion criteria |
•Other forms of lung cancer (eg, small cell, mesothelioma)
•Women who are pregnant or breast-feeding
•Had major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patients must be well recovered from acute effects of surgery prior to screening. Patients should not have plans to undergo major surgical procedures during the treatment period.
•Patients unable to readily swallow oral tablets. Patients with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption, or obstructive symptoms) or intractable or frequent vomiting are excluded
•Has untreated clinically relevant hypothyroidism
•Has known or symptomatic brain metastases |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Lean Body Mass change from baseline as measured by DXA
2. Hand Grip Strength of the non-dominant hand change from baseline |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Lean Body Mass change from baseline as measured by DXA over 12 weeks
2. Hand Grip Strength of the non-dominant hand change over 12 weeks |
|
E.5.2 | Secondary end point(s) |
1. Percentage change in Lean Body Mass
2. Percentage change on Hand Grip Strength of the non-dominant hand
3. Changes in body weight
4. Change in Hand Grip Strength of the dominant hand
5. Quality of life
6. Overall survival
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Percentage change in Lean Body mass over 12 weeks
2. Percentage change on Hand Grip Strength of the non-dominant hand over 12 weeks
3. Changes in body weight at Weeks 3, 6, 9, 12
4. Change in Hand Grip strength of the dominant hand at Weeks 6, 12
5. Quality of life as assessed by FAACT and FACIT-F at Weeks 3, 6, 9, 12
6. Overall survival assessed until death up to 1 year
|
|
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Hungary |
Israel |
Poland |
Russian Federation |
United Kingdom |
United States |
|
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
|
Patients will be followed for 1 year from randomization (every 3 months) for survival status. Patients who enter the extension study (HT-ANAM-303) will continue to participate in the survival follow-up for this study. |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |