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Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01387269
Recruitment Status : Completed
First Posted : July 4, 2011
Results First Posted : July 11, 2017
Last Update Posted : October 27, 2017
Sponsor:
Information provided by (Responsible Party):
Helsinn Therapeutics (U.S.), Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Cachexia
Non-Small Cell Lung Cancer
Interventions Drug: Anamorelin HCl
Drug: Placebo
Enrollment 484
Recruitment Details Approximately 477 patients with advanced NSCLC-C (defined as unresectable Stage III and Stage IV and a weight loss of ≥ 5% body weight within 6 months prior to screening or a screening body mass index [BMI] < 20 kg/m2) were to be randomized 2:1 to anamorelin HCl 100 mg or placebo.
Pre-assignment Details Central randomization stratified patients by geographic region, by chemotherapy and/or radiation therapy status and by weight loss over prior 6 months.
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Period Title: Overall Study
Started 323 161
ITT Population 323 161
MITT Population 284 141
Safety Population 320 161
Completed [1] 231 121
Not Completed 92 40
Reason Not Completed
Death             38             20
Other             8             7
Unrelated AE             12             3
Withdrawal by patient             32             10
Study drug-related AE             1             0
Lost to Follow-up             1             0
[1]
A patient was considered to have completed the study if the patient completed Week 12/Day 85 Visit.
Arm/Group Title Anamorelin HCl Placebo Total
Hide Arm/Group Description Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. Total of all reporting groups
Overall Number of Baseline Participants 323 161 484
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) Population included all randomized patients.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 161 participants 484 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
215
  66.6%
105
  65.2%
320
  66.1%
>=65 years
108
  33.4%
56
  34.8%
164
  33.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 161 participants 484 participants
Female
76
  23.5%
40
  24.8%
116
  24.0%
Male
247
  76.5%
121
  75.2%
368
  76.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 161 participants 484 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.3%
0
   0.0%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.3%
0
   0.0%
1
   0.2%
White
319
  98.8%
159
  98.8%
478
  98.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   0.6%
2
   1.2%
4
   0.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 323 participants 161 participants 484 participants
Russian Federation 8 4 12
Serbia 10 3 13
Ukraine 133 66 199
Belarus 15 9 24
United States 26 11 37
Canada 9 6 15
Netherlands 2 0 2
Poland 48 26 74
Slovenia 5 4 9
Spain 13 3 16
Belgium 11 4 15
Czech Republic 16 11 27
France 8 6 14
Germany 10 3 13
Italy 9 5 14
Geographic region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants 161 participants 484 participants
North America
35
  10.8%
17
  10.6%
52
  10.7%
West Europe
122
  37.8%
62
  38.5%
184
  38.0%
East Europe + Russia
166
  51.4%
82
  50.9%
248
  51.2%
Australia
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change in Lean Body Mass
Hide Description Change in Lean Body Mass (LBM) from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.
Time Frame Change in Lean Body Mass from Baseline Over 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Some patients in the ITT population were excluded from the primary LBM/HGS analysis (i.e., multiple imputations/ranking method) if they survived to Week 12 but missed their baseline covariates including LBM, HGS, or ECOG OR had Week 6 and Week 12 outcomes that were outside the visit windows.
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description:
Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Number of Participants Analyzed 316 158
Median (95% Confidence Interval)
Unit of Measure: kg
0.99
(0.61 to 1.36)
-0.47
(-1.00 to 0.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anamorelin HCl, Placebo
Comments Superiority analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
2.Primary Outcome
Title Change in Handgrip Strength
Hide Description Change in Handgrip Strength (HGS) of the non-dominant hand from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.
Time Frame Change in Handgrip Strength of the Non-Dominant Hand from Baseline Over 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Some patients in the ITT population were excluded from the primary LBM/HGS analysis (i.e., multiple imputations/ranking method) if they survived to Week 12 but missed their baseline covariates including LBM, HGS, or ECOG OR had Week 6 and Week 12 outcomes that were outside the visit windows.
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description:
Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Number of Participants Analyzed 316 158
Median (95% Confidence Interval)
Unit of Measure: kg
-1.10
(-1.69 to -0.40)
-1.58
(-2.99 to -1.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anamorelin HCl, Placebo
Comments Superiority analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1475
Comments [Not Specified]
Method Wilcoxon rank sum test
Comments [Not Specified]
3.Secondary Outcome
Title Change in A/CS Domain Score
Hide Description

The Functional Assessment of Anorexia/Cachexia Treatment (FAACT) Additional Concerns Subscale (A/CS domain) is a 12-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much).

The 12-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the A/CS domain ranges from 0 (worst) to 48 (best).

Time Frame Change in FAACT A/CS Domain Score from Baseline Over 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description:
Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Number of Participants Analyzed 284 141
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
4.12  (0.752) 1.92  (0.805)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anamorelin HCl, Placebo
Comments Superiority analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Change in FACIT-F Fatigue Domain Score
Hide Description

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue domain is a 13-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much).

The 13-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the FACIT-F fatigue domain ranges from 0 (worst) to 52 (best).

Time Frame Change in FACIT-F Fatigue Domain Score from Baseline Over 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description:
Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Number of Participants Analyzed 284 141
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
0.26  (0.886) -1.19  (0.933)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anamorelin HCl, Placebo
Comments Superiority analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0544
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Change in Body Weight
Hide Description Change in body weight (BW) from baseline overall (i.e., over 12 weeks) for the MITT Population.
Time Frame Change in Body Weight from Baseline Over 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description:
Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
Overall Number of Participants Analyzed 284 141
Least Squares Mean (Standard Error)
Unit of Measure: kg
2.20  (0.326) 0.14  (0.363)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anamorelin HCl, Placebo
Comments Superiority analysis
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame Adverse events that occurred during the clinical trial, commenced with the first dose of study drug through the 28 day post-treatment follow-up visit.
Adverse Event Reporting Description Adverse events that occurred following the signature of the informed consent, but prior to the first dose of study drug were not reported as adverse events in this trial. The adverse event reporting period also ended if the patient began an alternative therapy within 28 days of the last administration of study drug. The Safety Population, defined as all randomized patients who received any study drug, was used for all safety analyses.
 
Arm/Group Title Anamorelin HCl Placebo
Hide Arm/Group Description Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.
All-Cause Mortality
Anamorelin HCl Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Anamorelin HCl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   82/320 (25.62%)      48/161 (29.81%)    
Blood and lymphatic system disorders     
Anaemia  1  5/320 (1.56%)  6 3/161 (1.86%)  3
Febrile neutropenia  1  0/320 (0.00%)  0 3/161 (1.86%)  3
Neutropenia  1  2/320 (0.63%)  2 1/161 (0.62%)  1
Pancytopenia  1  3/320 (0.94%)  3 1/161 (0.62%)  1
Thrombocytopenia  1  1/320 (0.31%)  1 3/161 (1.86%)  3
Leukocytosis  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Idiopathic thrombocytopenic purpura  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Leukopenia  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Cardiac disorders     
Pericardial effusion  1  2/320 (0.63%)  2 1/161 (0.62%)  1
Arrhythmia  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Cardiac arrest  1  0/320 (0.00%)  0 2/161 (1.24%)  2
Myocardial infarction  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Atrial flutter  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Cardiopulmonary failure  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Atrial fibrillation  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Ischaemic cardiomyopathy  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Rectal haemorrhage  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Gastrointestinal ulcer  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Dysphagia  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Gastrointestinal haemorrhage  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Oesophagitis  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Colitis ischaemic  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Abdominal pain  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Nausea  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Vomiting  1  2/320 (0.63%)  2 0/161 (0.00%)  0
Gastric haemorrhage  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Small intestinal obstruction  1  1/320 (0.31%)  1 0/161 (0.00%)  0
General disorders     
Death  1  2/320 (0.63%)  2 1/161 (0.62%)  1
General physical health deterioration  1  3/320 (0.94%)  3 1/161 (0.62%)  1
Pain  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Pyrexia  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Asthenia  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Fatigue  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Hepatobiliary disorders     
Hepatic failure  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Cholecystitis  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Infections and infestations     
Pneumonia  1  4/320 (1.25%)  4 4/161 (2.48%)  5
Cellulitis  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Urinary tract infection  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Respiratory tract infection  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Bronchopulmonary aspergillosis  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Staphylococcal infection  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Lung infection  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Gastroenteritis  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Lobar pneumonia  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Sepsis  1  2/320 (0.63%)  2 0/161 (0.00%)  0
Oral candidiasis  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Bronchopneumonia  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Osteomyelitis acute  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Hepatitis C  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  3/320 (0.94%)  3 0/161 (0.00%)  0
Failure to thrive  1  0/320 (0.00%)  0 2/161 (1.24%)  2
Decreased appetite  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Dehydration  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Hypocalcaemia  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Diabetes mellitus  1  2/320 (0.63%)  2 0/161 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  1/320 (0.31%)  1 1/161 (0.62%)  1
Musculoskeletal chest pain  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Bone pain  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression  1  24/320 (7.50%)  24 12/161 (7.45%)  12
Nervous system disorders     
Presyncope  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Ischaemic stroke  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Psychiatric disorders     
Mental status changes  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Agitation  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Renal and urinary disorders     
Urinary tract obstruction  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Renal failure  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  4/320 (1.25%)  5 3/161 (1.86%)  4
Pulmonary embolism  1  3/320 (0.94%)  3 0/161 (0.00%)  0
Pulmonary haemorrhage  1  3/320 (0.94%)  3 1/161 (0.62%)  1
Dyspnoea  1  0/320 (0.00%)  0 2/161 (1.24%)  3
Respiratory failure  1  0/320 (0.00%)  0 2/161 (1.24%)  2
Bronchopulmonary hemorrhage  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Haemoptysis  1  0/320 (0.00%)  0 1/161 (0.62%)  1
Epistaxis  1  2/320 (0.63%)  2 0/161 (0.00%)  0
Dyspnoea exertional  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Pleuritic pain  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Iliac artery occlusion  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Inferior vena caval occlusion  1  1/320 (0.31%)  1 0/161 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Anamorelin HCl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   182/320 (56.88%)      84/161 (52.17%)    
Blood and lymphatic system disorders     
Anaemia  1  119/320 (37.19%)  179 66/161 (40.99%)  114
Leukopenia  1  16/320 (5.00%)  17 10/161 (6.21%)  10
Neutropenia  1  28/320 (8.75%)  34 22/161 (13.66%)  34
Thrombocytopenia  1  29/320 (9.06%)  42 23/161 (14.29%)  34
Gastrointestinal disorders     
Diarrhoea  1  17/320 (5.31%)  21 9/161 (5.59%)  9
Nausea  1  29/320 (9.06%)  44 15/161 (9.32%)  21
Vomiting  1  25/320 (7.81%)  27 8/161 (4.97%)  8
General disorders     
Asthenia  1  19/320 (5.94%)  23 9/161 (5.59%)  10
Fatigue  1  25/320 (7.81%)  28 13/161 (8.07%)  15
Pyrexia  1  15/320 (4.69%)  16 1/161 (0.62%)  1
Investigations     
Alanine aminotransferase increased  1  50/320 (15.63%)  78 14/161 (8.70%)  20
Aspartate aminotransferase increased  1  37/320 (11.56%)  52 15/161 (9.32%)  21
Blood alkaline phosphatase increased  1  34/320 (10.63%)  40 10/161 (6.21%)  14
Platelet count decreased  1  14/320 (4.38%)  30 10/161 (6.21%)  16
Metabolism and nutrition disorders     
Decreased appetite  1  13/320 (4.06%)  15 8/161 (4.97%)  8
Hyperglycaemia  1  35/320 (10.94%)  41 10/161 (6.21%)  11
Respiratory, thoracic and mediastinal disorders     
Cough  1  14/320 (4.38%)  14 8/161 (4.97%)  9
Dyspnoea  1  19/320 (5.94%)  24 11/161 (6.83%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor intends to publish the complete study results in a timely manner that is appropriate to the project. Separate publication of a portion of the study results by any PI is discouraged.
Results Point of Contact
Name/Title: Richard K. Bourne, Ph.D.
Organization: Helsinn Therapeutics (US), Inc.
Phone: 732-603-2852
Responsible Party: Helsinn Therapeutics (U.S.), Inc
ClinicalTrials.gov Identifier: NCT01387269     History of Changes
Other Study ID Numbers: HT-ANAM-301
First Submitted: June 30, 2011
First Posted: July 4, 2011
Results First Submitted: March 15, 2017
Results First Posted: July 11, 2017
Last Update Posted: October 27, 2017