The Role of Ghrelin in Cancer Cachexia

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT01505764
• Collaborator: Helsinn Therapeutics (U.S.), Inc (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Cancer is often coupled with a condition called cachexia. In this condition, individuals continue to lose weight and lean body mass, which means their muscles are getting smaller and weaker. Studies have shown that cancer patients who are losing weight often are responding poorly to chemotherapy, are at greater risk of infection and have a reduced life expectancy. Also, people may not want to eat. To date, there are no approved treatments available for this condition.

This study is going to study the benefits of the use of the study drug, Anamorelin hydrochloride (HCl) in treatment or prevention of cachexia associated with cancer. Studies done before with the study drug have shown that the drug can help the cachectic condition. The purpose of this research study is to evaluate the effectiveness of Anamorelin HCl compared to placebo on body composition (amount of cell mass, fat, muscle, etc.) including measurements of body potassium and nitrogen stores.

In addition to the above, the study will also assess the effect of the study drug on handgrip strength, body weight, lean muscle mass, quality of life, appetite & food intake, certain blood markers, energy expenditure (the amount of energy participants burn), functional performance, safety and tolerability of Anamorelin HCl.

Condition or Disease	Intervention/Treatment	Phase
Cancer Cachexia	Drug: Anamorelin HCl; Drug: Placebo	Phase 2

Detailed Description

Subjects enrolled in the study will be randomly chosen to receive either Anamorelin HCL at a dose of 100 mg per day for 12 weeks or matching placebo. The chances of receiving anamorelin or placebo are 1 in 2. Which subject receives anamorelin or placebo will be decided at random. Neither the subject nor the study doctor will know which study drug the subject is receiving. The subject will be asked to visit the clinic at Day 1, Day 28, Day 56 and Day 84. There will also be a Day 112 follow-up visit and the medical records will be checked after that to see how the subjects are doing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Role of Ghrelin in Cancer Cachexia
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 (Anamorelin HCl) Anamorelin HCl	Drug: Anamorelin HCl; 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.
Placebo Comparator: Arm 2 (Placebo) Placebo	Drug: Placebo; Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.

Outcome Measures

Primary Outcome Measures

1. Total Body Potassium. [day 84]

   percentage change from baseline

Secondary Outcome Measures

1. Lean Mass Measured by Densitometry. [day 84]

   lean body mass measured by DEXA. Percentage of change day 84-baseline.

2. Muscle Strength as Measured by Grip Strength. [day 84]

   Dominant hand grip strength day 84 - percent change from baseline

3. Body Weight. [day 84]

   percent change from day 84-baseline

4. Quality of Life. [day 84]

   Quality of life as assessed using the FACIT-F Patient Reported Outcome assessments - percentage of change day 84-baseline

5. Appetite. [day 84]

   Appetite measured by a visual analogue scale ASAS. Percentage of change day84-baseline

6. Resting Energy Expenditure. [day 84]

   % change between day 84 and baseline

7. Functional Performance. [day 84]

   Functional performance using stair-climbing power day 84 percent change from baseline

8. Body Composition. [day 84]

   Body composition as measured by Total body nitrogen. Percentage of change day 84-baseline

9. Stair Climbing Power [day 84]

   Percent change from baseline

10. 1-repetition Max. Strength [day 84]

    leg extension - percentage of change day 84 to baseline

11. Food Diary Calorie Count [day 84]

    change between day 84 and baseline

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must have incurable, histologically or cytologically documented Non-Small Cell Lung Cancer or Colo-rectal Cancer.

• Females and males at least 18 years of age.

• Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) unresectable Stage III or IV NSCLC and/or stage III or IV colorectal cancer (CRC) (not amenable to curative resection).

• Involuntary weight loss of 5% body weight over a period of 6 months.

• Eastern Cooperative Oncology Group (ECOG) performance status 2 at screening.

• Estimated life expectancy of greater than 4 months at the time of screening.

• Presence and functional use of both hands.

• Able to understand and comply with the procedures of the handgrip strength evaluation.

• If the patient is a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 28 days following the last dose of study medication.

• 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:

• Other forms of lung cancer.

• Women who are pregnant or breast-feeding.

• Obesity.

• Recent active excessive alcohol or illicit drug use current use of marijuana or history of marijuana use over the previous 6 months.

• Severe depression.

• Other causes of cachexia such as:

• Liver disease (AST or ALT > 3x normal levels)

• Renal failure (creatinine > 2.5 mg/dL)

• Untreated thyroid disease

• Class III-IV CHF

• AIDS

• Other cancer diagnosed within the past five years other than non-melanoma skin cancer and prostate cancer

• Severe COPD requiring use of home O2.

• Inability to increase food intake.

• Recent administration of highly emetogenic chemotherapy.

• Known HIV, active hepatitis B or C (with increased LFTs), or active tuberculosis.

• Patients who have received two prior regimens of cytotoxic chemotherapy and are undergoing, or planning to undergo, a third regimen of cytotoxic chemotherapy.

• 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

• Dronabinol

• Current use of steroids or history of use over the previous 6 months except as pre- and post-medications for chemotherapy administration.

• Patients unable to readily swallow oral tablets.

• An active, uncontrolled infection.

• Uncontrolled diabetes mellitus.

• Known or suspected brain metastases.

• Patients receiving strong CYP3A4 inhibitors.

• Patients receiving tube feedings or parenteral nutrition.

• Patients with any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements, including the inability to comply with handgrip strength determinations in both hands; for example, pre-existing neurological impairment.

• Previous exposure to Anamorelin HCl.

• Patients actively receiving a concurrent investigational agent, or any patients that have received an investigational agent within four weeks prior to randomization.

• Current use of diuretics or history of intermittent diuretic usage for any reason over the previous 3 months.

• History of claustrophobia.

• Cachexia deemed by the investigator to be solely due to chemo or radiation treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas	United States	77030

Sponsors and Collaborators

• VA Office of Research and Development
• Helsinn Therapeutics (U.S.), Inc

Investigators

• Principal Investigator: Jose M. Garcia, MD PhD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01505764
• Other Study ID Numbers: CLIN-013-08F; HT-ANAM-208
• First Posted: Jan 9, 2012
• Last Update Posted: Jul 17, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by VA Office of Research and Development: Cachexia
• Additional relevant MeSH terms: Wasting Syndrome; Cachexia

Study Results

Participant Flow

Recruitment Details	10 subjects were consented, 9 received drug or placebo, 5 completed the study.

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Period Title: Overall Study
STARTED	6	3
COMPLETED	3	2
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)	Total
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.	Total of all reporting groups
Overall Participants	6	4	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 83.3%	3 75%	8 80%
>=65 years	1 16.7%	1 25%	2 20%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	58	57
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 25%	2 20%
Male	5 83.3%	3 75%	8 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	0 0%	1 10%
Not Hispanic or Latino	5 83.3%	4 100%	9 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 16.7%	0 0%	1 10%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 33.3%	2 50%	4 40%
White	3 50%	2 50%	5 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	4 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Total Body Potassium.
Description	percentage change from baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	-2.13 (5.48)	-0.72 (2.11)

2. Secondary Outcome

Title	Lean Mass Measured by Densitometry.
Description	lean body mass measured by DEXA. Percentage of change day 84-baseline.
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

only two subjects in each group completed this measure.

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	2	2
Mean (Standard Deviation) [percentage change]	2.12 (3.05)	-1.44 (0.5)

3. Secondary Outcome

Title	Muscle Strength as Measured by Grip Strength.
Description	Dominant hand grip strength day 84 - percent change from baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

Cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	0.31 (11.19)	-10.45 (14.49)

4. Secondary Outcome

Title	Body Weight.
Description	percent change from day 84-baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	1.7 (3.19)	-1.8 (0.07)

5. Secondary Outcome

Title	Quality of Life.
Description	Quality of life as assessed using the FACIT-F Patient Reported Outcome assessments - percentage of change day 84-baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	-6.54 (4.9)	-14.32 (3.78)

6. Secondary Outcome

Title	Appetite.
Description	Appetite measured by a visual analogue scale ASAS. Percentage of change day84-baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	8.33 (38.18)	1.66 (25.92)

7. Secondary Outcome

Title	Resting Energy Expenditure.
Description	% change between day 84 and baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	-1.02 (13.8)	-2.58 (2.75)

8. Secondary Outcome

Title	Functional Performance.
Description	Functional performance using stair-climbing power day 84 percent change from baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

only two subjects in each group completed this measure.

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	2	2
Mean (Standard Deviation) [percentage change]	22.53 (9.87)	-13.8 (12.36)

9. Secondary Outcome

Title	Body Composition.
Description	Body composition as measured by Total body nitrogen. Percentage of change day 84-baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

only two subjects in each group completed this outcome

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	2	2
Mean (Standard Deviation) [percentage change]	-5.7 (3.4)	6.31 (4.2)

10. Secondary Outcome

Title	Stair Climbing Power
Description	Percent change from baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

only two subjects in each group completed this outcome

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	2	2
Mean (Standard Deviation) [percentage change]	-30.39 (27.86)	4.12 (15.23)

11. Secondary Outcome

Title	1-repetition Max. Strength
Description	leg extension - percentage of change day 84 to baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

only two subjects in each group completed this outcome

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	2	2
Mean (Standard Deviation) [percentage change]	93.87 (70.53)	-8.29 (0.56)

12. Secondary Outcome

Title	Food Diary Calorie Count
Description	change between day 84 and baseline
Time Frame	day 84

Outcome Measure Data

Analysis Population Description

cancer cachexia patients

Arm/Group Title	Arm 1 (Anamorelin HCl)	Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.	Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
Measure Participants	3	2
Mean (Standard Deviation) [percentage change]	-21 (14)	-12 (19)

Adverse Events

Arm/Group Title	Arm 1 (Anamorelin HCl)		Arm 2 (Placebo)
Arm/Group Description	Anamorelin HCl: 100 mg tablets; oral administration every day for 84 days, at least 1 hour before the first meal of the day.		Placebo: Placebo tablets identical in appearance to active tablets; oral administration once a day for 84 days, at least 1 hour before the first meal of the day.
All Cause Mortality
	Arm 1 (Anamorelin HCl)		Arm 2 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 (Anamorelin HCl)		Arm 2 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		1/4 (25%)
Blood and lymphatic system disorders
anemia	1/6 (16.7%)	1	0/4 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neoplasm progression	2/6 (33.3%)	2	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
respiratory failure	0/6 (0%)	0	1/4 (25%)	1
pneumonia	1/6 (16.7%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1 (Anamorelin HCl)		Arm 2 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/4 (25%)
Musculoskeletal and connective tissue disorders
chest pain	0/6 (0%)	0	1/4 (25%)	1
Nervous system disorders
pain	1/6 (16.7%)	1	0/4 (0%)	0
fatigue	1/6 (16.7%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
cough	0/6 (0%)	0	1/4 (25%)	1
wheezing	1/6 (16.7%)	1	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.