Phase III Study of the Effect of GTx-024 on Muscle Wasting in Patients With Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: GTx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01355484
• Collaborator: (none)
• Enrollment: 321
• Locations: 27
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 11.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the investigational drug GTx-024 can help subjects with non-small cell lung cancer increase physical function and maintain or gain muscle, also called "lean body mass".

Condition or Disease	Intervention/Treatment	Phase
Muscle Wasting; Non Small Cell Lung Cancer	Drug: GTx-024; Drug: placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo controlled, multicenter, multinational efficacy and safety study in subjects with non small cell lung cancer (NSCLC). Subjects will be evenly randomized to placebo or GTx-024 prior to initiation of first line chemotherapy. The primary efficacy analysis will be based on total lean body mass and physical function.

Study Design

• Study Type: Interventional
• Actual Enrollment: 321 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase III, Randomized, Double-Blind, Placebo Controlled Study of the Effect of GTx-024 on Muscle Wasting in Patients With Non-Small Cell Lung Cancer on First Line Platinum Plus a Taxane Chemotherapy
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GTx-024 subject will receive GTx-024 treatment for the duration of the trial	Drug: GTx-024; subjects will be randomized to receive GTx-024 for the full duration of the trial.
Placebo Comparator: Placebo subject will receive placebo for the duration of the trial	Drug: placebo; subject will receive placebo for the duration of the trial

Outcome Measures

Primary Outcome Measures

1. Physical Function [Day 84]

   Measure is the percentage of subjects at day 84 with stair climb power change >=10% from their baseline value.

2. Lean Body Mass [Day 84]

   Measure is the percentage of subjects at day 84 with lean body mass change >=0% from their baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• give voluntary, signed informed consent in accordance with institutional policies

• be non-obese as defined as body mass index (BMI)< or = to 32 and weight <300 pounds (<136kg)

• have been diagnosed with Stage III or IV NSCLC

• be prior to first line chemotherapy

• planned first line chemotherapy regimen is platinum plus paclitaxel only or platinum plus docetaxel 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 <or=1

• Serum creatinine <or=2.0 mg/dL

• MALES - age >or= 30 years

• FEMALES - age >or=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 >or=6 months but <12 months they must have a serum FSH concentration of >or=50 mIU/mL and an estradiol concentration of <or=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 <or=4.0 ng/mL or a negative prostate biopsy (no prostate cancer)within 6 months of evaluation

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 (Nexavar) 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 cannabis) or any prescription medication intended to increase appetite or treat unintentional weight loss

• have a baseline stair climb time >or=30 seconds (mean of two stair climbs)

• Have active cancer, other than NSCLC, or non-melanoma carcinoma of the skin, within the previous two years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GTx Investigative Site	Birmingham	Alabama	United States	35211
2	GTx Investigative Site	Long Beach	California	United States	90813
3	GTx Investigative Site	Aventura	Florida	United States	33180
4	GTx Investigative Site	Miami	Florida	United States	33133
5	GTx Investigative Site	Orange City	Florida	United States	32763
6	GTx Investigative Site	Tampa	Florida	United States	33612
7	GTx Investigative Site	Decatur	Illinois	United States	62526
8	GTx Investigative Site	Peoria	Illinois	United States	61615
9	GTx Investigative Site	Skokie	Illinois	United States	60076
10	GTx Investigative Site	Indianapolis	Indiana	United States	46260
11	GTx Investigative Site	Ashland	Kentucky	United States	41101
12	GTx Investigative Site	Concord	Massachusetts	United States	01742
13	GTx Investigative Site	St Clair Shores	Michigan	United States	48081
14	GTx Investigative Site	Tupelo	Mississippi	United States	38801
15	GTx Investigative Site	Great Falls	Montana	United States	59405
16	GTx Investigative Site	Rochester	New York	United States	14642
17	GTx Investigative Site	Burlington	North Carolina	United States	27215
18	GTx Investigative Site	Flat Rock	North Carolina	United States	28731
19	GTx Investigative Site	Wilmington	North Carolina	United States	28401
20	GTx Investigative Site	Winston Salem	North Carolina	United States	27103
21	GTx Investigative Site	Canfield	Ohio	United States	44406
22	Gabrail Cancer Center	Canton	Ohio	United States	44718
23	GTx Investigative Site	Sandusky	Ohio	United States	44870
24	GTx Investigative Site	Portland	Oregon	United States	97213
25	GTx Investigative Site	Lancaster	Pennsylvania	United States	17604
26	GTx Investigative Site	Spartanburg	South Carolina	United States	29303
27	GTx Investigative Site	Round Rock	Texas	United States	78665

Sponsors and Collaborators

• GTx

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GTx
• ClinicalTrials.gov Identifier: NCT01355484
• Other Study ID Numbers: G300504; POWER1
• First Posted: May 18, 2011
• Last Update Posted: Mar 3, 2016
• Last Verified: Feb 1, 2016

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Muscular Atrophy; Wasting Syndrome; Cachexia

Study Results

Participant Flow

Arm/Group Title	GTx-024	Placebo
Arm/Group Description	subject will receive GTx-024 treatment for the duration of the trial GTx-024: subjects will be randomized to receive GTx-024 for the full duration of the trial.	subject will receive placebo for the duration of the trial placebo: subject will receive placebo for the duration of the trial
Period Title: Overall Study
STARTED	160	161
COMPLETED	109	107
NOT COMPLETED	51	54

Baseline Characteristics

Arm/Group Title	GTx-024	Placebo	Total
Arm/Group Description	subject will receive GTx-024 treatment for the duration of the trial GTx-024: subjects will be randomized to receive GTx-024 for the full duration of the trial.	subject will receive placebo for the duration of the trial placebo: subject will receive placebo for the duration of the trial	Total of all reporting groups
Overall Participants	160	161	321
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.5	62.0	61.0
Sex: Female, Male (Count of Participants)
Female	43 26.9%	46 28.6%	89 27.7%
Male	117 73.1%	115 71.4%	232 72.3%

Outcome Measures

1. Primary Outcome

Title	Physical Function
Description	Measure is the percentage of subjects at day 84 with stair climb power change >=10% from their baseline value.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

Subjects included in the Full Analysis Set

Arm/Group Title	GTx-024	Placebo
Arm/Group Description	subject will receive GTx-024 treatment for the duration of the trial GTx-024: subjects will be randomized to receive GTx-024 for the full duration of the trial.	subject will receive placebo for the duration of the trial placebo: subject will receive placebo for the duration of the trial
Measure Participants	160	161
Number (95% Confidence Interval) [percentage of subjects]	29.4	24.2

2. Primary Outcome

Title	Lean Body Mass
Description	Measure is the percentage of subjects at day 84 with lean body mass change >=0% from their baseline value.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

Subjects included in the Full Analysis Set

Arm/Group Title	GTx-024	Placebo
Arm/Group Description	subject will receive GTx-024 treatment for the duration of the trial GTx-024: subjects will be randomized to receive GTx-024 for the full duration of the trial.	subject will receive placebo for the duration of the trial placebo: subject will receive placebo for the duration of the trial
Measure Participants	160	161
Number (95% Confidence Interval) [percentage of subjects]	41.9	30.4

Adverse Events

Time Frame	1 year, 7 months
Adverse Event Reporting Description	Initiation: 26 Oct 2011, Completion: 8 May 2013
Arm/Group Title	GTx-024		Placebo
Arm/Group Description	subject will receive GTx-024 treatment for the duration of the trial GTx-024: subjects will be randomized to receive GTx-024 for the full duration of the trial.		subject will receive placebo for the duration of the trial placebo: subject will receive placebo for the duration of the trial
All Cause Mortality
	GTx-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GTx-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/160 (35%)		60/161 (37.3%)
Blood and lymphatic system disorders
Anaemia	4/160 (2.5%)	4	5/161 (3.1%)	5
Neutropenia	3/160 (1.9%)	4	4/161 (2.5%)	6
Febrile Neutropenia	4/160 (2.5%)	4	2/161 (1.2%)	2
Thrombocytopenia	1/160 (0.6%)	1	1/161 (0.6%)	1
Granulocytopenia	1/160 (0.6%)	1	0/161 (0%)	0
Leukopenia	1/160 (0.6%)	1	0/161 (0%)	0
Lymphopenia	0/160 (0%)	0	1/161 (0.6%)	1
Cardiac disorders
Atrial Fibrillation	2/160 (1.3%)	2	0/161 (0%)	0
Cardiac Failure	1/160 (0.6%)	1	1/161 (0.6%)	1
Cardio-Respiratory Arrest	1/160 (0.6%)	1	0/161 (0%)	0
Cardiopulmonary Failure	1/160 (0.6%)	1	0/161 (0%)	0
Myocardial Infarction	0/160 (0%)	0	1/161 (0.6%)	1
Myocarditis	0/160 (0%)	0	1/161 (0.6%)	1
Supraventricular Tachycardia	0/160 (0%)	0	1/161 (0.6%)	1
Gastrointestinal disorders
Nausea	1/160 (0.6%)	1	2/161 (1.2%)	2
Vomiting	1/160 (0.6%)	1	1/161 (0.6%)	1
Diarrhoea	0/160 (0%)	0	1/161 (0.6%)	1
Duodenal Ulcer	1/160 (0.6%)	1	0/161 (0%)	0
Dysphagia	1/160 (0.6%)	1	0/161 (0%)	0
Gastric Haemorrhage	0/160 (0%)	0	1/161 (0.6%)	1
Gastroduodenitis	0/160 (0%)	0	1/161 (0.6%)	1
Oesophagitis	0/160 (0%)	0	1/161 (0.6%)	1
Upper Gastrointestinal Haemorrhage	1/160 (0.6%)	1	0/161 (0%)	0
General disorders
Disease Progression	19/160 (11.9%)	20	16/161 (9.9%)	16
Condition Aggravated	1/160 (0.6%)	1	2/161 (1.2%)	2
Death	0/160 (0%)	0	2/161 (1.2%)	2
General Physical Health Deterioration	1/160 (0.6%)	1	0/161 (0%)	0
Non-Cardiac Chest Pain	1/160 (0.6%)	1	0/161 (0%)	0
Infections and infestations
Pneumonia	6/160 (3.8%)	6	4/161 (2.5%)	4
Urinary Tract Infection	1/160 (0.6%)	1	1/161 (0.6%)	1
Abdominal Abscess	0/160 (0%)	0	1/161 (0.6%)	1
Bronchitis	0/160 (0%)	0	1/161 (0.6%)	1
Diverticulitis	0/160 (0%)	0	1/161 (0.6%)	1
Infectious Pleural Effusion	1/160 (0.6%)	1	0/161 (0%)	0
Neutropenic Sepsis	0/160 (0%)	0	1/161 (0.6%)	1
Respiratory Tract Infection	1/160 (0.6%)	1	0/161 (0%)	0
Staphylococcal Sepsis	0/160 (0%)	0	1/161 (0.6%)	1
Viral Infection	1/160 (0.6%)	1	0/161 (0%)	0
Injury, poisoning and procedural complications
Radiation Oesophagitis	1/160 (0.6%)	1	1/161 (0.6%)	1
Lower Limb Fracture	1/160 (0.6%)	1	0/161 (0%)	0
Open Fracture	1/160 (0.6%)	1	0/161 (0%)	0
Radiation Injury	0/160 (0%)	0	1/161 (0.6%)	1
Radiation Pneumonitis	1/160 (0.6%)	1	0/161 (0%)	0
Subdural Haematoma	1/160 (0.6%)	1	0/161 (0%)	0
Investigations
Neutrophil Count Decreased	1/160 (0.6%)	1	1/161 (0.6%)	1
Metabolism and nutrition disorders
Dehydration	1/160 (0.6%)	1	6/161 (3.7%)	7
Hypoglycaemia	1/160 (0.6%)	1	0/161 (0%)	0
Hyponatraemia	1/160 (0.6%)	1	0/161 (0%)	0
Hypovolaemia	1/160 (0.6%)	1	0/161 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Bone	1/160 (0.6%)	1	0/161 (0%)	0
Metastases To Central Nervous System	1/160 (0.6%)	1	0/161 (0%)	0
Metastases To Liver	0/160 (0%)	0	1/161 (0.6%)	1
Metastases To Meninges	0/160 (0%)	0	1/161 (0.6%)	1
Metastatic Pain	0/160 (0%)	0	1/161 (0.6%)	1
Nervous system disorders
Syncope	2/160 (1.3%)	2	0/161 (0%)	0
Cerebral Infarction	1/160 (0.6%)	1	0/161 (0%)	0
Cerebrovascular Accident	1/160 (0.6%)	1	0/161 (0%)	0
Psychiatric disorders
Completed Suicide	1/160 (0.6%)	1	0/161 (0%)	0
Delusional Disorder, Persecutory Type	0/160 (0%)	0	1/161 (0.6%)	1
Renal and urinary disorders
Renal Failure	1/160 (0.6%)	1	0/161 (0%)	0
Urinary Retention	0/160 (0%)	0	1/161 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	2/160 (1.3%)	2	4/161 (2.5%)	4
Dyspnoea	3/160 (1.9%)	4	2/161 (1.2%)	3
Haemoptysis	3/160 (1.9%)	3	2/161 (1.2%)	3
Pleural Effusion	2/160 (1.3%)	2	1/161 (0.6%)	1
Pulmonary Embolism	2/160 (1.3%)	2	1/161 (0.6%)	1
Pulmonary Haemorrhage	0/160 (0%)	0	3/161 (1.9%)	3
Chronic Obstructive Pulmonary Disease	0/160 (0%)	0	2/161 (1.2%)	2
Pneumothorax	1/160 (0.6%)	1	1/161 (0.6%)	1
Hydropneumothorax	1/160 (0.6%)	1	0/161 (0%)	0
Surgical and medical procedures
Abdominal Operation	1/160 (0.6%)	1	0/161 (0%)	0
Vascular disorders
Dee Vein Thrombosis	0/160 (0%)	0	3/161 (1.9%)	3
Jugular Vein Thrombosis	1/160 (0.6%)	1	0/161 (0%)	0
Orthostatic Hypertension	0/160 (0%)	0	1/161 (0.6%)	1
Subclavian Artery Thrombosis	0/160 (0%)	0	1/161 (0.6%)	1
Superior Vena Cava Syndrome	0/160 (0%)	0	1/161 (0.6%)	1
Thrombosis	0/160 (0%)	0	1/161 (0.6%)	1
Venous Thrombosis	1/160 (0.6%)	1	0/161 (0%)	0
Other (Not Including Serious) Adverse Events
	GTx-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	141/160 (88.1%)		144/161 (89.4%)
Blood and lymphatic system disorders
Anaemia	46/160 (28.8%)	60	44/161 (27.3%)	62
Neutropenia	20/160 (12.5%)	33	30/161 (18.6%)	44
Gastrointestinal disorders
Nausea	57/160 (35.6%)	118	52/161 (32.3%)	130
Vomiting	29/160 (18.1%)	39	26/161 (16.1%)	38
Diarrhoea	18/160 (11.3%)	33	24/161 (14.9%)	32
Constipation	17/160 (10.6%)	19	11/161 (6.8%)	14
General disorders
Disease Progression	22/160 (13.8%)	24	32/161 (19.9%)	36
Asthenia	33/160 (20.6%)	43	20/161 (12.4%)	31
Fatigue	20/160 (12.5%)	36	22/161 (13.7%)	30
Pyrexia	12/160 (7.5%)	14	14/161 (8.7%)	18
Chest Pain	8/160 (5%)	10	12/161 (7.5%)	13
Infections and infestations
Pneumonia	8/160 (5%)	8	14/161 (8.7%)	15
Metabolism and nutrition disorders
Decreased Appetite	11/160 (6.9%)	21	27/161 (16.8%)	45
Musculoskeletal and connective tissue disorders
Arthralgia	27/160 (16.9%)	49	22/161 (13.7%)	42
Myalgia	13/160 (8.1%)	24	10/161 (6.2%)	21
Pain In Extremity	13/160 (8.1%)	26	9/161 (5.6%)	19
Nervous system disorders
Peripheral Sensory Neuropathy	19/160 (11.9%)	23	9/161 (5.6%)	12
Neuropathy Peripheral	10/160 (6.3%)	19	8/161 (5%)	10
Respiratory, thoracic and mediastinal disorders
Dyspnoea	21/160 (13.1%)	31	12/161 (7.5%)	16
Cough	11/160 (6.9%)	12	14/161 (8.7%)	18
Haemoptysis	7/160 (4.4%)	9	14/161 (8.7%)	17
Skin and subcutaneous tissue disorders
Alopecia	54/160 (33.8%)	58	52/161 (32.3%)	62

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Provide Sponsor with an advance copy of any proposed results communication at least 60 days prior to the date of the planned submission or presentation and Sponsor shall have 60 days from receipt to request any changes. Sponsor may request a delay of up to 60 additional days. The PI shall not present data until the earlier of Sponsor's publication of the results of all investigators participating in the Study or 18 months after completion of the Study at all participating sites.