Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 2)

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: NCT01387282
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 495
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 330 165
ITT Population 330 165
MITT Population 268 136
Safety Population 330 161
Completed [1] 233 118
Not Completed 97 47
Reason Not Completed
Death             47             16
Other             5             1
Unrelated AE             6             4
Withdrawal by patient             33             23
Study drug-related AE             2             2
Lost to Follow-up             4             1
[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 330 165 495
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 165 participants 495 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
209
  63.3%
108
  65.5%
317
  64.0%
>=65 years
121
  36.7%
57
  34.5%
178
  36.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 165 participants 495 participants
Female
90
  27.3%
43
  26.1%
133
  26.9%
Male
240
  72.7%
122
  73.9%
362
  73.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 165 participants 495 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   0.6%
1
   0.2%
Native Hawaiian or Other Pacific Islander
1
   0.3%
0
   0.0%
1
   0.2%
Black or African American
2
   0.6%
1
   0.6%
3
   0.6%
White
326
  98.8%
162
  98.2%
488
  98.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.3%
1
   0.6%
2
   0.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 330 participants 165 participants 495 participants
Poland 133 70 203
United Kingdom 1 0 1
Hungary 72 36 108
Australia 14 8 22
Israel 8 5 13
Russian Federation 92 41 133
United States 10 5 15
Geographic region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 165 participants 495 participants
North America
10
   3.0%
5
   3.0%
15
   3.0%
West Europe
142
  43.0%
75
  45.5%
217
  43.8%
East Europe + Russia
164
  49.7%
77
  46.7%
241
  48.7%
Australia
14
   4.2%
8
   4.8%
22
   4.4%
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 321 157
Median (95% Confidence Interval)
Unit of Measure: kg
0.65
(0.38 to 0.91)
-0.98
(-1.49 to -0.41)
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 321 157
Median (95% Confidence Interval)
Unit of Measure: kg
-1.49
(-2.06 to -0.58)
-0.95
(-1.56 to 0.04)
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 0.6480
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 268 136
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
3.48  (0.944) 1.34  (1.032)
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 0.0016
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 268 136
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
1.37  (1.169) 1.23  (1.293)
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 0.8637
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 268 136
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.95  (0.386) -0.57  (0.438)
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   --/--      --/--    
Hide Serious Adverse Events
Anamorelin HCl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   73/330 (22.12%)      27/161 (16.77%)    
Blood and lymphatic system disorders     
Anaemia  1  3/330 (0.91%)  3 3/161 (1.86%)  3
Neutropenia  1  2/330 (0.61%)  2 1/161 (0.62%)  1
Febrile neutropenia  1  2/330 (0.61%)  2 2/161 (1.24%)  2
Pancytopenia  1  2/330 (0.61%)  2 0/161 (0.00%)  0
Thrombocytopenia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Agranulocytosis  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Pulmonary haemorrhage  1  5/330 (1.52%)  5 0/161 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  1/330 (0.30%)  1 1/161 (0.62%)  1
Atrial tachycardia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Tachycardia paroxysmal  1  1/330 (0.30%)  1 0/161 (0.00%)  0
cardiopulmonary failure  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Cardiac failure congestive  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Gastrointestinal disorders     
Nausea  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Vomiting  1  2/330 (0.61%)  2 0/161 (0.00%)  0
Abdominal pain  1  0/330 (0.00%)  0 1/161 (0.62%)  1
General disorders     
Death  1  3/330 (0.91%)  3 0/161 (0.00%)  0
Pyrexia  1  3/330 (0.91%)  3 0/161 (0.00%)  0
General physical health deterioration  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Infections and infestations     
Pneumonia  1  6/330 (1.82%)  6 0/161 (0.00%)  0
Sepsis  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Tuberculosis  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Viral infection  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Bronchitis  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Infective exacerbation of chronic obstructive airways disease  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Gastroenteritis  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Injury, poisoning and procedural complications     
Head injury  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Fall  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Investigations     
Blood creatine increased  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Blood glucose increased  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Dehydration  1  1/330 (0.30%)  1 1/161 (0.62%)  1
Electrolyte imbalance  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Diabetes mellitus  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Diabetes mellitus inadequate control  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Hypokalaemia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Hyperkalaemia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Hypertriglyceridaemia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Hypercalcaemia  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression  1  25/330 (7.58%)  25 10/161 (6.21%)  10
Gastric cancer  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Epiglottic carcinoma  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Nervous system disorders     
Convulsion  1  1/330 (0.30%)  1 1/161 (0.62%)  1
cerebrovasculary insufficiency  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Cerebrovascular accident  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Psychiatric disorders     
Completed suicide  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Confusional state  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Renal and urinary disorders     
Haematuria  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/330 (0.30%)  1 1/161 (0.62%)  1
Pulmonary embolism  1  4/330 (1.21%)  4 0/161 (0.00%)  0
Pneumothorax  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Haemoptysis  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Lower respiratory tract infection  1  2/330 (0.61%)  2 0/161 (0.00%)  0
Vascular disorders     
Circulatory collapse  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Hypotension  1  0/330 (0.00%)  0 1/161 (0.62%)  1
Extremity necrosis  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Peripheral arterial occlusive disease  1  1/330 (0.30%)  1 0/161 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
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   156/330 (47.27%)      72/161 (44.72%)    
Blood and lymphatic system disorders     
Anaemia  1  48/330 (14.55%)  61 21/161 (13.04%)  28
Leukopenia  1  25/330 (7.58%)  29 6/161 (3.73%)  7
Neutropenia  1  31/330 (9.39%)  48 10/161 (6.21%)  14
Gastrointestinal disorders     
Nausea  1  19/330 (5.76%)  20 13/161 (8.07%)  13
Vomiting  1  9/330 (2.73%)  11 9/161 (5.59%)  12
General disorders     
Asthenia  1  29/330 (8.79%)  30 16/161 (9.94%)  19
Metabolism and nutrition disorders     
Hyperglycaemia  1  23/330 (6.97%)  32 3/161 (1.86%)  3
Skin and subcutaneous tissue disorders     
Alopecia  1  29/330 (8.79%)  35 14/161 (8.70%)  15
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
Layout table for Results Point of Contact information
Name/Title: Richard K. Bourne, Ph.D.
Organization: Helsinn Therapeutics (US), Inc.
Phone: 732-603-2852
EMail: richard.bourne@helsinn.com
Layout table for additonal information
Responsible Party: Helsinn Therapeutics (U.S.), Inc
ClinicalTrials.gov Identifier: NCT01387282    
Other Study ID Numbers: HT-ANAM-302
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