Study of GTx-024 on Muscle Wasting (Cachexia) Cancer.

• Sponsor: GTx (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00467844
• Collaborator: (none)
• Enrollment: 159
• Locations: 52
• Arms: 3
• Duration (Months): 16.1
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess if Gtx-024 is effective in increasing lean body mass in subjects with muscle wasting related to cancer.

Condition or Disease	Intervention/Treatment	Phase
Cachexia	Drug: GTx-024; Drug: GTx-024; Drug: Placebo	Phase 2

Detailed Description

Cancer cachexia is characterized by a hypermetabolic state that leads to catabolism that is responsible for reductions in lean mass.These catabolic changes are accompanied by an increase in total energy expenditure, but a decrease in voluntary energy expenditure that ultimately results clinically in cachexia and its symptoms of lethargy, fatigue, weakness and general malaise (Kotler DP. Cachexia. Ann Intern Med. 2000; 133:622-634).

The prevalence of cachexia increases from 50 percent at presentation to more than 80 percent before death from malignancy. In over 20 percent of cancer patients, cachexia is the cause of death (Bruera E. Anorexia, cachexia and nutrition. Br Med J 1997;315:1219-1222). Cancer cachexia leads to shorter survival, decreased response rates and increased toxicity to chemotherapy, weakness, and an overall decreased quality of life (DeWys et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980 Oct;69(4):491-7). The purpose of this study is to assess the efficacy of GTx-024 on total body lean mass. Secondary endpoints include but are not limited to assessment of GTx-024 on muscle function, total body weight and total body fat mass.

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Double-Blind, Placebo-Controlled, Dose-Finding Study of the Effect of GTx-024 on Muscle Wasting (Cachexia) in Patients With Cancer
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 1 mg GTx-024	Drug: GTx-024; 1 mg GTx 024
Experimental: 2 3 mg GTx-024	Drug: GTx-024; 3 mg GTx-024
Placebo Comparator: 3 Placebo	Drug: Placebo; Matching Placebo

Outcome Measures

Primary Outcome Measures

1. The Efficacy of GTx-024 on Total Body Lean Mass. [Baseline to Four Months]

   Change in total body lean mass as measured by dual energy x-ray absorptiometry (DEXA)from baseline to 4 months.

Secondary Outcome Measures

1. To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb. [Four Months]

   Change in stair climb power from baseline to 4 months. Stair climb power is defined power (watts)=[9.8 m/sec**2]*[weight (kg)]*[height of 12 steps(meters)]/ [time (seconds) up the 12 steps].

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be eligible for participation in this study, subjects must meet all of the following criteria:

• have been diagnosed with Stage 2, 3 or 4 non-small cell lung cancer or Stage 2, 3 or 4 colorectal cancer or non-hodgkin's lymphoma or chronic lymphocytic leukemia or Stage 3 or 4 breast cancer.

• be prior to initiation of or between cycles of chemotherapy.

• have experienced greater than or equal to 2% weight loss from the highest patient reported weight in the 6 months prior to screening for Protocol G200502 (Wt = body weight)

% weight loss = (Wt at screening - highest Wt in last 6 months) / highest Wt in last 6 months x 100%

• If surgery is part of the cancer treatment, screening for this study should be conducted at least 2 weeks (14 days) after surgery.

• have a life expectancy of >6 months

• FEMALES - be clinically confirmed as postmenopausal

• MALES - over 45 years of age

• ECOG score ≤1

Exclusion Criteria:

Subjects with any of the following will NOT be eligible for enrollment in this study:

• history of active/uncontrolled congestive heart failure, chronic hepatitis, hepatic cirrhosis, or HIV infection

• Cardiovascular: No uncontrolled hypertension

• Positive screen for Hepatitis B consisting of HBsAg (Hepatitis B Surface Antigen), anti-HCV (Hepatitis C Antibody), hepatitis A antibody IgM, or HIV

• Currently taking testosterone, OXANDRIN® (oxandrolone), testosterone-like agents (such as DHEA, androstenedione, and other androgenic compounds, including herbals), or antiandrogens (Please note that previous therapy with testosterone and testosterone-like agents is acceptable with a 30 day wash-out. However, if the previous testosterone therapy was a long-term depot, within the past 6 months, the site should call the medical monitor for this study to determine appropriate washout period.)

• Currently taking megestrol acetate (MEGACE®), dronabinol (MARINOL®), or any prescription medication intended to increase appetite or treat unintentional weight loss

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Cancer Research and Education Center	Anchorage	Alaska	United States	99508
2	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
3	Compassionate Cancer Care	Corona	California	United States	92882
4	Compassionate Cancer Care Medical Group	Fountain Valley	California	United States	92708
5	Pacific Coast Hematology/Oncology Medical Group, Inc.	Fountain Valley	California	United States	92708
6	Desert Hematology Oncology Medical Group	Rancho Mirage	California	United States	92270
7	Compassionate Cancer Care	Riverside	California	United States	92501
8	Penrose Cancer Center	Colorado Springs	Colorado	United States	80907
9	Dorcy Cancer Center	Pueblo	Colorado	United States	81004
10	Hartford Hospital Cancer Clinical Research Office	Hartford	Connecticut	United States	06102
11	Medical Oncology & Hematology, PC	Waterbury	Connecticut	United States	06708
12	Gainesville Hematology Oncology Associates	Gainesville	Florida	United States	32605
13	Horizon Institute for Clinical Research	Hollywood	Florida	United States	33021
14	Hematology Oncology Associates	Lake Worth	Florida	United States	33461
15	The Radiation Oncology Group	Lake Worth	Florida	United States	33461
16	Watson Clinic LLP, Center for Cancer Care & Research	Lakeland	Florida	United States	33805
17	Osler Medical	Melbourne	Florida	United States	32901
18	Innovative Medical Research of South Florida, Inc.	Miami	Florida	United States	33179
19	Florida Medical Clinic, PA	Zephyrhills	Florida	United States	33542
20	Augusta Oncology Associates	Augusta	Georgia	United States	30901
21	Dublin Hematology and Oncology	Dublin	Georgia	United States	31021
22	Cancer Center of Kansas	Wichita	Kansas	United States	67214
23	Kentuckiana Cancer Institute	Louisville	Kentucky	United States	40202
24	Johns Hopkins University Clinical Trial Unit	Baltimore	Maryland	United States	21287
25	Center for Cancer & Blood Disorders	Bethesda	Maryland	United States	20817
26	The Center for Clinical Research WA County Hospital	Hagerstown	Maryland	United States	21740
27	Newland Medical Center	Southfield	Michigan	United States	48075
28	The West Clinic	Corinth	Mississippi	United States	38834
29	West Clinic	Corinth	Mississippi	United States	38834
30	The West Clinic	Southaven	Mississippi	United States	38671
31	West Clinic	Southaven	Mississippi	United States	38671
32	Hematology & Oncology Associates at Bridgeport	Tupelo	Mississippi	United States	38801
33	Heartland Hematology-Oncology Associates	Kansas City	Missouri	United States	64118
34	Donald H. Berdeaux, MD, FACP, PC	Great Falls	Montana	United States	59405
35	Great Falls Clinic, LLP - Clinic Cancer Care	Great Falls	Montana	United States	59405
36	Creighton University Hematology/Oncology Clinic	Omaha	Nebraska	United States	68131
37	Cancer Care of Western North Carolina	Ashville	North Carolina	United States	28801
38	Four Seasons Hospice & Palliative Care	Flat Rock	North Carolina	United States	28731
39	Hanover Medical Specialists	Wilmington	North Carolina	United States	28401
40	Gabrail Cancer Center	Canton	Ohio	United States	44718
41	Signal Point Clinical Research Center, LLC	Middletown	Ohio	United States	45042
42	Hematology Oncology Consultants	Worthington	Ohio	United States	43235
43	Consultants in Medical Oncology and Hematology	Drexel Hill	Pennsylvania	United States	19026
44	Urological Associates of Lancaster	Lancaster	Pennsylvania	United States	17604
45	Berks Hematology-Oncology Associates	West Reading	Pennsylvania	United States	19611
46	Charleston Hematology Oncology Associates	Charleston	South Carolina	United States	29403
47	West Clinic	Memphis	Tennessee	United States	38104
48	West Clinic	Memphis	Tennessee	United States	38120
49	Dallas Oncology Consultants	Dallas	Texas	United States	75237
50	Providence Everett Medical Center, Cancer Research Department	Everett	Washington	United States	98201
51	University of Alberta Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
52	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• GTx

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GTx
• ClinicalTrials.gov Identifier: NCT00467844
• Other Study ID Numbers: G200502; NCT00832104
• First Posted: May 1, 2007
• Last Update Posted: Jul 11, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by GTx: Cachexia; Muscle Wasting; Non-Small Cell Lung Cancer; Colorectal Cancer; Non-Hodgkin's Lymphoma; Stage 3 or 4 Breast Cancer; Chronis Lymphocytic Leukemia
• Additional relevant MeSH terms: Muscular Atrophy; Wasting Syndrome; Cachexia

Study Results

Participant Flow

Arm/Group Title	GTx -024	GTx-024	3 mg of Placebo
Arm/Group Description	1 mg	3 mg	Placebo
Period Title: Overall Study
STARTED	53	54	52
COMPLETED	34	34	38
NOT COMPLETED	19	20	14

Baseline Characteristics

Arm/Group Title	GTx -024	GTx-024	3 mg of Placebo	Total
Arm/Group Description	1 mg	3 mg	Placebo	Total of all reporting groups
Overall Participants	53	54	52	159
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	25 47.2%	22 40.7%	24 46.2%	71 44.7%
>=65 years	28 52.8%	32 59.3%	28 53.8%	88 55.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.7 (10.03)	66.3 (10.51)	65.6 (8.73)	65.9 (9.74)
Sex: Female, Male (Count of Participants)
Female	19 35.8%	20 37%	17 32.7%	56 35.2%
Male	34 64.2%	34 63%	35 67.3%	103 64.8%
Region of Enrollment (participants) [Number]
United States	39 73.6%	37 68.5%	36 69.2%	112 70.4%
Argentina	14 26.4%	17 31.5%	16 30.8%	47 29.6%

Outcome Measures

1. Primary Outcome

Title	The Efficacy of GTx-024 on Total Body Lean Mass.
Description	Change in total body lean mass as measured by dual energy x-ray absorptiometry (DEXA)from baseline to 4 months.
Time Frame	Baseline to Four Months

Outcome Measure Data

Analysis Population Description

The number of participants were those subjects in the modified intent-to-treat population (defined as subjects with at least one post baseline DEXA for LBM) who had baseline and 4 month DEXA results for LBM (observed cases).

Arm/Group Title	GTx-024 1 mg	GTx-024 3 mg	Placebo
Arm/Group Description	Placebo
Measure Participants	32	34	34
Median (Full Range) [kg]	1.55	0.98	0.02

2. Secondary Outcome

Title	To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb.
Description	Change in stair climb power from baseline to 4 months. Stair climb power is defined power (watts)=[9.8 m/sec**2]*[weight (kg)]*[height of 12 steps(meters)]/ [time (seconds) up the 12 steps].
Time Frame	Four Months

Outcome Measure Data

Analysis Population Description

The subjects were in the MITT population (had a post baseline DEXA) and had a month 4 stair climb assessment (observed cases).

Arm/Group Title	GTx -024	GTx-024	3 mg of Placebo
Arm/Group Description	1 mg	3 mg	Placebo
Measure Participants	31	28	36
Median (Full Range) [watts]	19.93	12.84	11.34

Adverse Events

Arm/Group Title	GTx -024		GTx-024		3 mg of Placebo
Arm/Group Description	1 mg		3 mg		Placebo
All Cause Mortality
	GTx -024		GTx-024		3 mg of Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	GTx -024		GTx-024		3 mg of Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/53 (26.4%)		15/54 (27.8%)		17/52 (32.7%)
Blood and lymphatic system disorders
Anaemia	3/53 (5.7%)		0/54 (0%)	0	0/52 (0%)	0
Febrile Neutropenia	2/53 (3.8%)		0/54 (0%)	0	3/52 (5.8%)	0
Neutropenia	1/53 (1.9%)		1/54 (1.9%)		0/52 (0%)	0
Pancytopenia	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
Thrombocytopenia	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
Cardiac disorders
Atrial Fibrillation	1/53 (1.9%)		0/54 (0%)	0	0/52 (0%)	0
Myocardial infarction	1/53 (1.9%)		0/54 (0%)	0	0/52 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/53 (1.9%)		0/54 (0%)	0	0/52 (0%)	0
Dysphagia	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
gastric ulcer perforation	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
lower gastrointestinal haemorrhage	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
pancreatitis	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
rectal obstruction	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
small intestinal obstruction	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
upper gastrointestinal haemorrhage	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
Infections and infestations
cellulitis	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
diverticulitis	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
pneumonia	2/53 (3.8%)		3/54 (5.6%)		2/52 (3.8%)
sepsis	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
septic shock	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
staphylococcal skin infection	0/53 (0%)	0	0/54 (0%)	0	1/52 (1.9%)	0
Injury, poisoning and procedural complications
compression fracture	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
hip fracture	1/53 (1.9%)		0/54 (0%)	0	0/52 (0%)	0
patella fracture	1/53 (1.9%)		0/54 (0%)	0	1/52 (1.9%)	0
road traffic accident	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
Therapeutic agent toxicity	0/53 (0%)	0	0/54 (0%)	0	0/52 (0%)	0
Metabolism and nutrition disorders
diabetes mellitus	1/53 (1.9%)	1	0/54 (0%)	0	0/52 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
lung neoplasm malignant	0/53 (0%)	0	0/0 (NaN)	0	1/52 (1.9%)	1
malignant neoplasm progression	5/53 (9.4%)	6	7/54 (13%)	6	8/52 (15.4%)	9
Metastases to central nervous system	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
metastatic pain	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
non small cell lung cancer	1/53 (1.9%)	1	0/54 (0%)	0	1/52 (1.9%)	1
Nervous system disorders
brain stem infarction	1/53 (1.9%)	1	0/54 (0%)	0	0/52 (0%)	0
Renal and urinary disorders
renal failure acute	1/53 (1.9%)	1	0/54 (0%)	0	0/52 (0%)	0
Respiratory, thoracic and mediastinal disorders
acute pulmonary oedema	1/53 (1.9%)	1	0/54 (0%)	0	0/52 (0%)	0
chronic obstructive pulmonary disease	0/53 (0%)	0	1/54 (1.9%)	0	0/52 (0%)	0
dyspnoea	1/53 (1.9%)	1	0/54 (0%)	0	0/52 (0%)	0
Other (Not Including Serious) Adverse Events
	GTx -024		GTx-024		3 mg of Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/53 (88.7%)		49/54 (90.7%)		46/52 (88.5%)
Blood and lymphatic system disorders
anaemia	13/53 (24.5%)		7/54 (13%)		8/52 (15.4%)
neutropenia	3/53 (5.7%)		5/54 (9.3%)		2/52 (3.8%)
thrombocytopenia	3/53 (5.7%)		5/54 (9.3%)		3/52 (5.8%)
Gastrointestinal disorders
abdominal pain	2/53 (3.8%)		8/54 (14.8%)		3/52 (5.8%)
constipation	9/53 (17%)		6/54 (11.1%)		2/52 (3.8%)
diarrhoea	8/53 (15.1%)		9/54 (16.7%)		7/52 (13.5%)
vomiting	9/53 (17%)		4/54 (7.4%)		6/52 (11.5%)
asthenia	1/53 (1.9%)		7/54 (13%)		4/52 (7.7%)
fatigue	8/53 (15.1%)		14/54 (25.9%)		11/52 (21.2%)
Nausea	13/53 (24.5%)		6/54 (11.1%)		7/52 (13.5%)
General disorders
pyrexia	5/53 (9.4%)		8/54 (14.8%)		3/52 (5.8%)
Infections and infestations
pneumonia	2/53 (3.8%)		4/54 (7.4%)		2/52 (3.8%)
Investigations
weight decreased	5/53 (9.4%)		8/54 (14.8%)		5/52 (9.6%)
Metabolism and nutrition disorders
anorexia	5/53 (9.4%)	5	6/54 (11.1%)	5	2/52 (3.8%)	2
dehydration	1/53 (1.9%)	1	7/54 (13%)	7	6/52 (11.5%)	6
Musculoskeletal and connective tissue disorders
back pain	5/53 (9.4%)	5	1/54 (1.9%)	1	3/52 (5.8%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
malignant neoplasm progression	6/53 (11.3%)	8	8/54 (14.8%)	8	8/52 (15.4%)	9
Nervous system disorders
headache	3/53 (5.7%)	3	5/54 (9.3%)	7	1/52 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
cough	2/53 (3.8%)	2	9/54 (16.7%)	9	6/52 (11.5%)	6
dyspnoea	7/53 (13.2%)	8	4/54 (7.4%)	6	5/52 (9.6%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.