Effects of Anamorelin on Cancer-Related-Fatigue in Patients With Advanced Cancer

Baseline Tests:

If after the screening procedures and pregnancy test (if applicable) you are found to be
eligible to take part in this study, you will be asked to:

- You will have a physical exam.

- Blood (about 1 teaspoon) will be drawn for routine tests and cytokine testing. Cytokines
are proteins that may affect the immune system.

- You will complete 9 questionnaires about your symptoms, emotional and physical health,
level of fatigue, appetite, sleep, and regular exercise habits. It should take about 50
minutes to complete all questionnaires.

- You will meet with an exercise specialist to discuss your current strength and fitness
level.

- You will meet with a dietitian for nutritional support. You will have your resting
energy expenditure (REE) measured to see how much oxygen you use at rest. To measure
your REE, you will hold a device called a calorimeter and will breathe into the
mouthpiece for 5 minutes. You will have your body mass index (BMI) measured while you
stand on a scale and hold a device for about 20 seconds.

- You will complete a 6-minute walk test where you will be timed while you walk a 100-foot
loop as many times as you can.

- You will complete a chair-stand test where you will sit in a chair and stand and sit
down as many times as you can in 30 seconds.

- You will be taught how to do resistance exercises to complete at home.

Study Drug Administration:

You will take anamorelin by mouth 1 time each day for 6 weeks, preferably in the evening. You
will need to fast (have nothing to eat or drink except water) for at least 1 hour before the
dose, each time.

Tracking your Diet:

As part of this study, you may be asked to track your food intake (diet). You may choose do
so in 1 of 2 ways: you can track this information by using a paper diary provided by the
study staff or by downloading a free smartphone application (app) called MyFitnessPal (MFP).
Your format for tracking this information is up to you. However, if you do not have a
smartphone, no phone will be provided, and you will need to use the paper option.

If you choose to track your diet using MFP, a study-specific MFP account will be set up for
you by the study staff. You will be asked to enter your food and drink intake into the MFP
app each time you eat or drink and note the time (using the "diary notes" feature). The study
staff can show you how to use the app. The app will not receive any of your protected health
information. However, you should review all privacy permissions related to using the app
before downloading.

Physical Activities:

You will be asked to complete resistance exercises and a walking program at home for 6 weeks
while also taking anamorelin.

You will be given an accelerometer to wear while exercising for 5 days before each study
visit. An accelerometer is a small device that measures your physical activity. You can clip
the accelerometer to your waistband or belt.

For the resistance exercises, you will use color-coded tubes that have 3 levels of
resistance: light, moderate, or hard. You will begin with 1 set of 10-12 repetitions at the
lightest resistance and progress to 2 sets of 12 repetitions as you get stronger. Once you
have mastered a resistance level, you will move up in resistance as your strength and
endurance increases. You should begin the next level of resistance with 2 sets of 12
repetitions. You will complete these exercises 3 days a week with at least 48 hours between
each session.

For the walking program, you will be asked to walk at least 5 days per week. The study staff
will recommend how long each walk should be and how many times to walk each day.

You will wear a pedometer at all times while you are on study. A pedometer is a device that
shows the number of steps you have taken. You will receive instructions on how to use the
pedometer. You will also receive a diary to record the number of steps you take each day. You
should bring this diary to each study visit.

Length of Study:

You will receive anamorelin while performing the physical activities for 6 weeks.

If you and the doctor think it is in your best interest, you may continue to take the study
drug for an additional 6 weeks and repeat all study visits and procedures. You will no longer
be able to take the study drug or perform the physical activities as part of this study if
the disease gets worse, if intolerable side effects occur, or if you are unable to follow
study directions.

Your participation on the study will be over after the follow-up period.

Study Visits:

One (1) time each week, on or about Days 8, 15, 29, and 36, you will be called to ask about
your physical activity progress and how you are doing. These calls should last about 10-15
minutes each time.

On or about Days 8, 15, 21, 29, 36, and 43, you will complete the same 8 questionnaires that
you completed at baseline.

On or about Days 15, 29, and 43 you will complete a questionnaire about any symptoms you may
be having. This questionnaire should take about 5 minutes to complete each time.

On or about Day 21, you will meet with an exercise specialist to discuss your physical
activity progress and a dietitian for nutrition counseling. If you have difficulty tasting
food, you will be given zinc oxide and amino acids to take every day for 4 weeks to help
increase your appetite. Blood (about 1 tablespoon) will be drawn for routine and cytokine
testing, and to check your liver function and fasting blood glucose levels.

On or about Day 29, you will complete a questionnaire about your sleep quality in the past 30
days. This questionnaire should take about 10 minutes to complete.

On or about Day 43:

- You will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine and cytokine testing, and to check
your liver function and fasting blood glucose levels.

- You will complete the same physical performance tests you did at baseline.

- You will complete 3 questionnaires about your regular exercise habits, your symptoms
after treatment, and sleep quality. It should take about 20 minutes to complete these
questionnaires.

- You will have your REE and BMI measured.

Follow-Up Period:

On or about Day 71, you will be called by a member of the study staff and asked about your
health. This call should last about 10 minutes.

Inclusion Criteria:

1. Patient with a diagnosis of advanced cancer (metastatic or recurrent incurable solid
tumors excluding prostate cancer)

2. Presence of fatigue on FACIT-F subscale of fatigue and 0 =worst possible fatigue)

3. Patient should describe fatigue as being present for a minimum of 2 weeks prior to
screening

4. CRP must be >/= 3mg/l* in the absence of any other more likely cause of increased CRP
like an infection or an autoimmune disorder.

5. No evidence of moderate to severe depression as determined by a HADS depression score
of
6. Presence of unintentional weight loss ranging from >/= 2 - the last 12 months

7. Uncontrolled pain; If patient is on opioids for the treatment of cancer pain, he/she
must have had no major dose change (>25%) for at least 48 hours prior to study entry.
The dose of morphine equivalent daily should not exceed 120mg/day unless approved by
the PI. Change in opioid dose after study entry is allowed;

8. Patient must be 18 years of age or older. The questionnaires used in this study have
been validated only in the adult population

9. Patient must be willing to engage in telephone follow up with research staff

10. Patient must have telephone access to be contacted by the research staff

11. Hemoglobin level of >/=9 g/dL

12. Estimated life expectancy of > 4 months at the time of screening

13. Adequate hepatic function, defined as aspartate transaminase (AST) and alanine
transaminase (ALT) levels
Exclusion Criteria:

1. Major contraindications to anamorelin e.g. hypersensitivity

2. Regularly engaged in moderate or vigorous-intensity exercise for at least 5 times a
week

3. Inability to complete the baseline assessment forms or to understand the
recommendations for participation in the study

4. Pregnant or lactating women, childbearing age women who are not on birth control.
Negative pregnancy test for women of childbearing potential, as defined by intact
uterus and ovaries, and a history of menses within the last 12 months. Pregnancy test
to be performed no greater than 14 days prior to consent in study. In cases of women
with elevated b-HCG, these candidates will be eligible to participate so long as the
level of b-HCG is not consistent with pregnancy. Women of childbearing potential need
to be on or use contraception, or be abstinent during the study period. Their male
partners must also use contraception (condom) or maintain abstinence. Birth controls
specifications: Women who are able to become pregnant must use birth control during
the study and for 30 days after the last Anamorelin dose. Acceptable forms of birth
control include barrier methods (such as condom or diaphragm) with spermicide.

5. Uncontrolled diabetes mellitus ( Fasting Blood Sugar >200mg/dl) at screening

6. Male patients with a history of untreated hypogonadism

7. Patients on drugs with strong CYP 3A4 inhibitors within the previous two weeks
(ketoconazole, clarithromycin, itraconazole, nefazodone, telithromycin)

8. Patients on drugs that may prolong the PR or QRS interval durations, such as any of
the Class I/Sodium (Na+) Channel blocking antiarrhythmic medications should be avoided
(e.g. Flecainide, Procainamide, Propafenone, Quinidine).

9. Patients with untreated clinically relevant hypothyroidism

10. Patients currently on investigational therapies will be evaluated by the PI on a case
by case basis and study participation approval will be obtained from the treating
oncologist.

11. Patients with prostate cancer