E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cachexia, muscle wasting in patients with Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Accelerated loss of skeletal muscle and body weight in patients with 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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025048 |
E.1.2 | Term | Lung cancer non-small cell recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the efficacy of GTx-024 on physical function
To assess the efficacy of GTx-024 on total LBM (overall LBM)
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E.2.2 | Secondary objectives of the trial |
- To assess the durability of effect of GTx-024 on physical function
- To assess the durability of effect of GTx-024 on total lean body mass (LBM)
- To assess the change from baseline in physical function in the GTx-024 treatment group compared to placebo
- To assess the change from baseline in total LBM in the GTx-024 treatment group compared to placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Give voluntary, signed informed consent in accordance with institutional policies
- Be non-obese as defined as body mass index (BMI) ≤ 32 and weight < 300 pounds (< 136 kg)
- Have been diagnosed with Stage III or IV NSCLC
- Be prior to first line chemotherapy
- Planned first line chemotherapy regimen is platinum plus gemcitabine only or platinum plus vinorelbine only or platinum plus pemetrexed only
- If surgery is part of the cancer treatment, screening for this study should be conducted at least 4 weeks (28 days) after surgery
- Life expectancy of > 6 months
- ECOG score ≤ 1
- Serum creatinine ≤ 2.0 mg/dL
- MALES – age ≥ 30 years
- FEMALES – age ≥ 30 years and clinically confirmed as postmenopausal. Subjects must have undergone the onset of spontaneous or surgical menopause prior to the start of this
study. Spontaneous menopause is defined as the natural cessation of ovarian function as indicated by being amenorrheic for at least 12 months. If the subject has been amenorrheic for >6 months but <12 months they must have a serum FSH concentration of ≥ 50 mIU/mL and an estradiol concentration of ≤ 25 pg/mL. Surgical menopause is
defined as bilateral oophorectomy.
- MALES – Subjects must agree to use a double barrier method of contraception during the study and for 3 months after study completion. This may include the following: condom + spermicide or condom + oral hormonal contraception
- MALES – have a serum PSA of ≤ 4.0 ng/mL or a negative prostate biopsy (no prostate cancer) within 6 months of evaluation |
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E.4 | Principal exclusion criteria |
- Have, in the judgment of the Investigator, a clinically significant concurrent illness or psychological, familial, sociological, geographical or other concomitant condition that would not permit adequate follow-up and compliance with the study protocol
- Have ALT/SGOT or AST/SGPT above 1.5 times the upper limit of normal (ULN) without evidence of liver metastases and above 5 times the ULN in subjects with evidence of liver metastases
- Have alkaline phosphatase greater than 3 times ULN and/or total bilirubin levels above 2 mg/dL at baseline
- Have biologic agents or kinase inhibitors as part of their first line chemotherapy regimen including, but not limited to bevacizumab (Avastin®), gefitinib (Iressa®) and erlotinib (Tarceva®)
- Cardiovascular: uncontrolled hypertension, congestive heart failure or angina
- Pulmonary: Stage 4 chronic obstructive pulmonary disease (COPD)
- Positive screen for Hepatitis B consisting of HBsAg (Hepatitis B Surface Antigen), unless subject was diagnosed > 10 years prior to enrollment and no evidence of active liver disease
- Positive screen for anti-HCV (Hepatitis C Antibody), hepatitis A antibody IgM, or HIV
- Currently taking testosterone, oxandrolone (Oxandrin®), testosterone-like agents (such as dehydroepiandrosterone (DHEA), androstenedione, and other androgenic compounds, including herbals), or antiandrogens; previous therapy with testosterone and
testosterone-like agents is acceptable with a 30 day washout (if previous testosterone therapy was long term depot within the past 6 months, the site should contact the medical monitor for this study to determine appropriate washout period)
- Currently taking megestrol acetate (Megace®), dronabinol (Marinol®), medical marijuana (medical cannibis) or any prescription medication intended to increase appetite or treat unintentional weight loss (any such products must be discontinued prior to randomization).
- Have a baseline stair climb time ≥ 30 seconds (mean of two stair climbs)
- Have active cancer, other than NSCLC or non-melanoma carcinoma of the skin, within previous two years |
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E.5 End points |
E.5.1 | Primary end point(s) |
Physical function will be ascertained by stair climb power (SCP) at Day 84. The percent change from baseline SCP will be computed to determine if the subject is a physical function responder. A subject is considered a responder if he/she has a Day 84 SCP assessment and at least a 10% increase in power compared to baseline. A subject is considered a nonresponder in physical function if they do not meet both of these criteria.
Total LBM at Day 84 will be ascertained. A subject is considered a responder if he/she has a Day 84 LBM assessment and no loss in LBM compared to baseline. A subject is considered a nonresponder in total LBM if they do not meet both of these criteria. |
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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) |
1. Physical function will be ascertained by SCP at Day 147 to determine if a subject who responded at Day 84 had a durable response to the physical function test
2. Total LBM will be ascertained at Day 147 to determine if a subject who responded at Day 84 had a durable response with respect to total LBM
3. Physical function will be ascertained by SCP at Day 84 to calculate each subject’s change in SCP from baseline and compute the mean change in SCP for each arm
4. Total LBM will be ascertained at Day 84 to calculate each subject’s change in LBM from baseline and compute the mean change in LBM for each arm
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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 | Yes |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Argentina |
Chile |
Hungary |
Peru |
Poland |
Russian Federation |
Ukraine |
United States |
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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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Day 147: Last visit of the last subject undergoing the trial;
After Day 147: the subjects will be followed for vital status. These data will be collected by chart review or by phone every one (1) month starting when the subject completes the Day 147/End of Study Intervention visit. The follow up period is expected to be up to 30 months from the start of this study (first patient first visit). |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |