Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): An Extension Study (ROMANA 3)

• Sponsor: Helsinn Therapeutics (U.S.), Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01395914
• Collaborator: (none)
• Enrollment: 513
• Locations: 72
• Arms: 2
• Duration (Months): 43.1
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The administration of Anamorelin HCl in patients with Non-Small Cell Lung Cancer-Cachexia (NSCLC-C) is expected to increase appetite, lean body mass, weight gain, and muscle strength.

Condition or Disease	Intervention/Treatment	Phase
Cachexia; Non-Small Cell Lung Cancer	Drug: Anamorelin HCl; Drug: Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, parallel-group, placebo-controlled, extension study to assess the safety and efficacy of Anamorelin HCl in NSCLC-C patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 513 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): An Extension Study
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 100 mg QD 100 mg yellow coated, oval tablet; oral administration once daily	Drug: Anamorelin HCl
Placebo Comparator: Placebo Placebo tablets identical in appearance to active tablets; oral administration once daily	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Treatment-emergent Adverse Events [Over the 12-week treatment period]

   To Evaluate the Safety and Tolerability of Anamorelin HCl.

Secondary Outcome Measures

1. Change in Body Weight [Change in body weight from baseline of the original trial through Week 12 of this extension trial.]

2. Change in Handgrip Strength of the Non-Dominant Hand [Change in HGS from baseline of the original trial through Week 12 of this extension trial.]

3. Change in A/CS Domain Score [Change in FAACT A/CS Domain Score from baseline of the original trial through Week 12 of this extension trial]

   Change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT) 12-item Additional Concerns Subscale (A/CS) domain score is a 12-item scale. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has completed the Day 85 Visit in the original trial (Study HT-ANAM-301 or HT-ANAM-302) and is considered appropriate to continue to receive additional study drug; must start dosing on the extension study within 5 days of completing dosing on the original trial

• ECOG performance status ≤2

• Life expectancy of >4 months at time of screening

• If woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 30 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method)

• Must be willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the protocol tests and procedures

Exclusion Criteria:

• Women who are pregnant or breast-feeding

• Had major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to enrollment into the extension study; patients must be well recovered from acute effects of surgery prior to screening; patients should not have plans to undergo major surgical procedures during the treatment period

• Currently taking prescription medications intended to increase appetite or treat weight loss; these include, but are not limited to, testosterone, androgenic compounds, megestrol acetate, methylphenidate, and dronabinol

• Inability to readily swallow oral tablets; patients with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption, or obstructive symptoms) or intractable or frequent vomiting are excluded

• Has an active, uncontrolled infection

• Has known or symptomatic brain metastases

• Receiving strong CYP3A4 inhibitors

• Receiving tube feedings or parenteral nutrition (either total or partial); patients must have discontinued these treatments for at least 6 weeks prior to Day 1, and throughout the study duration

• Other clinical diagnosis, ongoing or intercurrent illness that in the Investigator's opinion would prevent the patient's participation

• Patients actively receiving a concurrent investigational agent, other than Anamorelin HCl

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Corona	California	United States
2		Fountain Valley	California	United States
3		Fullerton	California	United States
4		Glendale	California	United States
5		La Jolla	California	United States
6		Riverside	California	United States
7		Washington, D.C.	District of Columbia	United States
8		Orange City	Florida	United States
9		Quincy	Illinois	United States
10		Indianapolis	Indiana	United States
11		Louisville	Kentucky	United States
12		Boston	Massachusetts	United States
13		Lake Success	New York	United States
14		Durham	North Carolina	United States
15		Cleveland	Ohio	United States
16		Sylvania	Ohio	United States
17		West Reading	Pennsylvania	United States
18		Charleston	South Carolina	United States
19		Falls Church	Virginia	United States
20		Prairiewood	New South Wales	Australia
21		Adelaide		Australia
22		East Bentleigh		Australia
23		Victoria		Australia
24		Brest		Belarus
25		Lesnoy		Belarus
26		Minsk		Belarus
27		Antwerpen		Belgium
28		Brussels		Belgium
29		Genk		Belgium
30		Gent		Belgium
31		Liege		Belgium
32		Edmonton	Alberta	Canada
33		Sault Ste Marie	Ontario	Canada
34		Toronto	Ontario	Canada
35		Montreal	Quebec	Canada
36		Benesov		Czechia
37		Brno		Czechia
38		Hlucin		Czechia
39		Liberec		Czechia
40		Nymburk		Czechia
41		Lyon Cedex		France
42		Villejuif cedex		France
43		Grosshansdorf		Germany
44		Halle		Germany
45		Budapest		Hungary
46		Kassai		Hungary
47		Beer-Sheva		Israel
48		Petach Tikvah		Israel
49		Tel-Hashomer		Israel
50		Zerifin		Israel
51		Piacenza		Italy
52		Bydgoszcz		Poland
53		Grudziadz		Poland
54		Katowice		Poland
55		Krakow		Poland
56		Lodz		Poland
57		Lublin		Poland
58		Szczecin		Poland
59		Warszawa		Poland
60		Ekaterinburg		Russian Federation
61		Krasnodar		Russian Federation
62		Moscow		Russian Federation
63		St. Petersburg		Russian Federation
64		Belgrade		Serbia
65		Sremska Kamenica		Serbia
66		Ljubljana		Slovenia
67		Barcelona		Spain
68		Sevilla		Spain
69		Valencia		Spain
70		Dnipropetrovsk		Ukraine
71		Kharkiv		Ukraine
72		Kyiv		Ukraine

Sponsors and Collaborators

• Helsinn Therapeutics (U.S.), Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Helsinn Therapeutics (U.S.), Inc
• ClinicalTrials.gov Identifier: NCT01395914
• Other Study ID Numbers: HT-ANAM-303
• First Posted: Jul 18, 2011
• Last Update Posted: Sep 14, 2017
• Last Verified: Aug 1, 2017

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

Study Results

Participant Flow

Recruitment Details	Patients who completed dosing in either of the original trials of anamorelin HCl in the treatment of NSCLC-C (HT-ANAM-301 or HT-ANAM-302) were able to enroll in this study and continue to receive the study drug to which they were assigned, either anamorelin HCl 100 mg or placebo QD for an additional 12 weeks.
Pre-assignment Detail	The primary purpose of this extension study was to permit patients who completed dosing in the original 12-week trials to have the option of continuing to receive randomized study drug for an additional 12 weeks, to further evaluate the safety and tolerability of anamorelin HCl.

Arm/Group Title	Anamorelin HCl	Placebo
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	345	168
ITT Population	345	168
Safety Population	343	167
COMPLETED	273	131
NOT COMPLETED	72	37

Baseline Characteristics

Arm/Group Title	Anamorelin HCl	Placebo	Total
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 Participants	345	168	513
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	236 68.4%	120 71.4%	356 69.4%
>=65 years	109 31.6%	48 28.6%	157 30.6%
Sex: Female, Male (Count of Participants)
Female	83 24.1%	43 25.6%	126 24.6%
Male	262 75.9%	125 74.4%	387 75.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 0.6%	1 0.2%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.2%
Black or African American	0 0%	0 0%	0 0%
White	344 99.7%	166 98.8%	510 99.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 0.6%	1 0.2%
Region of Enrollment (participants) [Number]
Poland	107 31%	60 35.7%	167 32.6%
Slovenia	0 0%	1 0.6%	1 0.2%
Spain	5 1.4%	2 1.2%	7 1.4%
Belgium	2 0.6%	2 1.2%	4 0.8%
Czech Republic	11 3.2%	3 1.8%	14 2.7%
France	1 0.3%	2 1.2%	3 0.6%
Germany	3 0.9%	0 0%	3 0.6%
Hungary	39 11.3%	16 9.5%	55 10.7%
Italy	1 0.3%	0 0%	1 0.2%
Netherlands	1 0.3%	0 0%	1 0.2%
Canada	3 0.9%	1 0.6%	4 0.8%
United States	16 4.6%	4 2.4%	20 3.9%
Belarus	8 2.3%	6 3.6%	14 2.7%
Israel	4 1.2%	2 1.2%	6 1.2%
Serbia	4 1.2%	2 1.2%	6 1.2%
Ukraine	64 18.6%	33 19.6%	97 18.9%
Russian Federation	69 20%	31 18.5%	100 19.5%
Australia	7 2%	3 1.8%	10 1.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events
Description	To Evaluate the Safety and Tolerability of Anamorelin HCl.
Time Frame	Over the 12-week treatment period

Outcome Measure Data

Analysis Population Description

Safety Population, defined as patients who received any extension trial study drug.

Arm/Group Title	Anamorelin HCl	Placebo
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.
Measure Participants	343	167
Number [percentage of participants]	52 15.1%	56 33.3%

2. Secondary Outcome

Title	Change in Body Weight
Time Frame	Change in body weight from baseline of the original trial through Week 12 of this extension trial.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population

Arm/Group Title	Anamorelin HCl	Placebo
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.
Measure Participants	345	168
Least Squares Mean (Standard Error) [kg]	3.06 (0.631)	0.92 (0.697)

3. Secondary Outcome

Title	Change in Handgrip Strength of the Non-Dominant Hand
Time Frame	Change in HGS from baseline of the original trial through Week 12 of this extension trial.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population

Arm/Group Title	Anamorelin HCl	Placebo
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.
Measure Participants	345	168
Least Squares Mean (Standard Error) [kg]	-0.83 (0.929)	-0.55 (1.036)

4. Secondary Outcome

Title	Change in A/CS Domain Score
Description	Change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT) 12-item Additional Concerns Subscale (A/CS) domain score is a 12-item scale. 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 of the original trial through Week 12 of this extension trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anamorelin HCl	Placebo
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.
Measure Participants	345	168
Least Squares Mean (Standard Error) [scores on a scale]	4.46 (0.92)	3.24 (1.01)

Adverse Events

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.
Arm/Group Title	Anamorelin HCl		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anamorelin HCl		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/343 (12.8%)		21/167 (12.6%)
Blood and lymphatic system disorders
Anaemia	3/343 (0.9%)	3	1/167 (0.6%)	1
Febrile neutropenia	1/343 (0.3%)	1	1/167 (0.6%)	1
Thrombocytopenia	1/343 (0.3%)	1	2/167 (1.2%)	2
Cardiac disorders
Angina unstable	1/343 (0.3%)	1	0/167 (0%)	0
Cardiopulmonary failure	0/343 (0%)	0	1/167 (0.6%)	1
Pericardial effusion	0/343 (0%)	0	1/167 (0.6%)	1
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/343 (0.3%)	1	0/167 (0%)	0
Gastrointestinal disorders
Duodenal ulcer	1/343 (0.3%)	1	0/167 (0%)	0
Gastric haemorrhage	1/343 (0.3%)	1	1/167 (0.6%)	1
Oesophagitis	1/343 (0.3%)	1	0/167 (0%)	0
Vomiting	1/343 (0.3%)	1	0/167 (0%)	0
General disorders
Asthenia	1/343 (0.3%)	1	1/167 (0.6%)	2
Death	1/343 (0.3%)	1	3/167 (1.8%)	3
Oedema peripheral	1/343 (0.3%)	1	0/167 (0%)	0
Multi-organ failure	1/343 (0.3%)	1	0/167 (0%)	0
Sudden death	1/343 (0.3%)	1	0/167 (0%)	0
Infections and infestations
Lower respiratory tract infection	1/343 (0.3%)	1	0/167 (0%)	0
Pneumonia	4/343 (1.2%)	4	0/167 (0%)	0
Injury, poisoning and procedural complications
Splenic rupture	1/343 (0.3%)	1	0/167 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/343 (0.3%)	1	0/167 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	1/343 (0.3%)	1	0/167 (0%)	0
Neoplasm progression	16/343 (4.7%)	16	7/167 (4.2%)	7
Tumour haemorrhage	1/343 (0.3%)	1	0/167 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/343 (0.3%)	1	0/167 (0%)	0
Convulsion	1/343 (0.3%)	1	0/167 (0%)	0
Nervous system disorder	1/343 (0.3%)	1	0/167 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/343 (0.3%)	1	0/167 (0%)	0
Chronic obstructive pulmonary disease	1/343 (0.3%)	1	0/167 (0%)	0
Dyspnoea	2/343 (0.6%)	2	1/167 (0.6%)	1
Pleural effusion	0/343 (0%)	0	1/167 (0.6%)	1
Pulmonary embolism	1/343 (0.3%)	1	0/167 (0%)	0
Respiratory failure	2/343 (0.6%)	2	1/167 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Anamorelin HCl		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/343 (27.4%)		57/167 (34.1%)
Blood and lymphatic system disorders
Anaemia	45/343 (13.1%)	56	25/167 (15%)	37
Neutropenia	18/343 (5.2%)	21	8/167 (4.8%)	8
General disorders
Asthenia	19/343 (5.5%)	20	14/167 (8.4%)	14
Metabolism and nutrition disorders
Decreased appetite	12/343 (3.5%)	13	10/167 (6%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.