Trial Outcomes & Findings for Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 2) (NCT NCT01387282)

Last Updated: 2017-10-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

495 participants

Primary outcome timeframe

Change in Lean Body Mass from Baseline Over 12 Weeks

Results posted on

2017-10-27

Participant Flow

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.

Central randomization stratified patients by geographic region, by chemotherapy and/or radiation therapy status and by weight loss over prior 6 months.

Participant milestones

Participant milestones
Measure	Anamorelin HCl Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo 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 Study STARTED	330	165
Overall Study ITT Population	330	165
Overall Study MITT Population	268	136
Overall Study Safety Population	330	161
Overall Study COMPLETED	233	118
Overall Study NOT COMPLETED	97	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Anamorelin HCl Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo 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 Study Death	47	16
Overall Study Other	5	1
Overall Study Unrelated AE	6	4
Overall Study Withdrawal by patient	33	23
Overall Study Study drug-related AE	2	2
Overall Study Lost to Follow-up	4	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anamorelin HCl n=330 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=165 Participants 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 n=495 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	209 Participants n=5 Participants	108 Participants n=7 Participants	317 Participants n=5 Participants
Age, Categorical >=65 years	121 Participants n=5 Participants	57 Participants n=7 Participants	178 Participants n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	43 Participants n=7 Participants	133 Participants n=5 Participants
Sex: Female, Male Male	240 Participants n=5 Participants	122 Participants n=7 Participants	362 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	326 Participants n=5 Participants	162 Participants n=7 Participants	488 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Poland	133 participants n=5 Participants	70 participants n=7 Participants	203 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Hungary	72 participants n=5 Participants	36 participants n=7 Participants	108 participants n=5 Participants
Region of Enrollment Australia	14 participants n=5 Participants	8 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Israel	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Russian Federation	92 participants n=5 Participants	41 participants n=7 Participants	133 participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Geographic region North America	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Geographic region West Europe	142 Participants n=5 Participants	75 Participants n=7 Participants	217 Participants n=5 Participants
Geographic region East Europe + Russia	164 Participants n=5 Participants	77 Participants n=7 Participants	241 Participants n=5 Participants
Geographic region Australia	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change in Lean Body Mass from Baseline Over 12 Weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=321 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=157 Participants 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.
Change in Lean Body Mass	0.65 kg Interval 0.38 to 0.91	-0.98 kg Interval -1.49 to -0.41

PRIMARY outcome

Timeframe: Change in Handgrip Strength of the Non-Dominant Hand from Baseline Over 12 Weeks

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.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=321 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=157 Participants 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.
Change in Handgrip Strength	-1.49 kg Interval -2.06 to -0.58	-0.95 kg Interval -1.56 to 0.04

SECONDARY outcome

Timeframe: Change in FAACT A/CS Domain Score from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

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).

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=268 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=136 Participants 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.
Change in A/CS Domain Score	3.48 scores on a scale Standard Error 0.944	1.34 scores on a scale Standard Error 1.032

SECONDARY outcome

Timeframe: Change in FACIT-F Fatigue Domain Score from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

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).

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=268 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=136 Participants 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.
Change in FACIT-F Fatigue Domain Score	1.37 scores on a scale Standard Error 1.169	1.23 scores on a scale Standard Error 1.293

SECONDARY outcome

Timeframe: Change in Body Weight from Baseline Over 12 Weeks

Population: Modified Intent-to-Treat Population

Change in body weight (BW) from baseline overall (i.e., over 12 weeks) for the MITT Population.

Outcome measures

Outcome measures
Measure	Anamorelin HCl n=268 Participants Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=136 Participants 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.
Change in Body Weight	0.95 kg Standard Error 0.386	-0.57 kg Standard Error 0.438

Adverse Events

Anamorelin HCl

Serious events: 73 serious events

Other events: 156 other events

Deaths: 0 deaths

Placebo

Serious events: 27 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Anamorelin HCl n=330 participants at risk Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day.	Placebo n=161 participants at risk 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.
Blood and lymphatic system disorders Anaemia	14.5% 48/330 • Number of events 61 • 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 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.	13.0% 21/161 • Number of events 28 • 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 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.
Blood and lymphatic system disorders Leukopenia	7.6% 25/330 • Number of events 29 • 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 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.	3.7% 6/161 • Number of events 7 • 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 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.
Blood and lymphatic system disorders Neutropenia	9.4% 31/330 • Number of events 48 • 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 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.	6.2% 10/161 • Number of events 14 • 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 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.
General disorders Asthenia	8.8% 29/330 • Number of events 30 • 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 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.	9.9% 16/161 • Number of events 19 • 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 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.
Gastrointestinal disorders Nausea	5.8% 19/330 • Number of events 20 • 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 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.	8.1% 13/161 • Number of events 13 • 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 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.
Gastrointestinal disorders Vomiting	2.7% 9/330 • Number of events 11 • 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 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.	5.6% 9/161 • Number of events 12 • 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 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.
Skin and subcutaneous tissue disorders Alopecia	8.8% 29/330 • Number of events 35 • 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 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.	8.7% 14/161 • Number of events 15 • 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 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.
Metabolism and nutrition disorders Hyperglycaemia	7.0% 23/330 • Number of events 32 • 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 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.	1.9% 3/161 • Number of events 3 • 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 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.

Additional Information

Richard K. Bourne, Ph.D.

Helsinn Therapeutics (US), Inc.

Phone: 732-603-2852

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER