Ginseng in Decreasing Cancer-Related Fatigue After Treatment in Cancer Survivors

PRIMARY OBJECTIVES:

I. To assess the efficacy of ginseng on decreasing cancer-related fatigue (CRF) in
post-treatment cancer survivors as measured by Multidimensional Fatigue Symptom Inventory
MFSI-Short Form (SF) at 28 and 56 days compared to placebo-controlled group.

SECONDARY OBJECTIVES:

I. To assess the acceptability and feasibility of ginseng as therapy for CRF in posttreatment
cancer survivors.

II. To evaluate toxicities and tolerability associated with 2,000 mg per day of North
American ginseng extract AFX-2 (panax quinquefolius) when used for cancer-related fatigue.

III. To explore the impact of ginseng on secondary endpoints, various dimensions of fatigue
as measured by the other subscales of the MFSI-SF, Patient-Reported Outcomes Measurement
Information System (PROMIS) Fatigue Short Form, as well as the single measure of fatigue
(captured on Fatigue Linear Analogue Scale).

IV. To determine clinically significant changes in fatigue scores per the various measures of
fatigue using the global impression of change.

TERTIARY OBJECTIVES:

I. To explore the relationship between ginseng therapy, inflammation biomarker adiponectin,
and post-treatment cancer survivors? fatigue.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP I: Patients receive North American ginseng extract AFX-2 orally (PO) twice daily (BID)
on days 1-28. Treatment repeats every 28 days for up to 2 courses in the absence of disease
progression or unacceptable toxicity.

GROUP II: Patients receive placebo PO BID on days 1-28. Treatment repeats every 28 days for
up to 2 courses in the absence of disease progression or unacceptable toxicity. At the end of
course 2, patients may optionally crossover to Group I to receive ginseng for an additional
28 days.

After completion of study, patients are followed up at day 28 and 56.

Inclusion Criteria:

- Histologic or cytologic proven breast cancer or colon cancer (stage I, II or III)

- Treated with chemotherapy and surgery

- Treatment has been completed (except hormone therapy) for >= 90 days prior to
registration

- No known evidence of disease

- Men or women with a history of CRF as defined by a score >= 4 on the numeric analogue
scale (0 ? 10) (Eligibility Question Fatigue Scale)

- Presence of CRF >= 30 days prior to registration

- Hemoglobin >= 11.0 g/dL obtained =< 180 days prior to registration

- Serum glutamic-oxaloacetic transaminase (SGOT) =< 1.5 x upper limit of normal (ULN)
obtained =< 180 days prior to registration

- Creatinine =< 1.2 X ULN obtained =< 180 days prior to registration

- Ability to complete questionnaire(s) in English by themselves or with assistance

- Provide written informed consent

- Willing to return to enrolling institution for follow-up of the study and optional
crossover (if applicable)

- Willing to provide blood samples for correlative research purposes

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- CROSSOVER RE-REGISTRATION - INCLUSION CRITERIA

- Treatment cannot begin prior to re-registering to the crossover phase and will ideally
begin =< 7 days after registration for the crossover phase

Exclusion Criteria:

- Hypersensitivity to ginseng

- Use of ginseng capsules for fatigue, within the last 12 months

- Uncontrolled hypertension >= 2 times as noted in medical history (diastolic blood
pressure > 100, systolic > 160) =< 90 days prior to registration

- Currently using any other pharmacologic agent to specifically treat fatigue including
psychostimulants, antidepressants, etc., although antidepressants used to treat items
other than fatigue (such as hot flashes) are allowed if the patient has been on a
stable dose for >= 30 days prior to registration and plans to continue for >= 30 days
after registration; erythropoietin agents to treat anemia are allowed

- Known brain metastasis or primary central nervous system (CNS) malignancy

- Chronic oral or intravenous systemic steroid use (defined as being used on a regular
basis or who have a problem that has required ongoing use of steroids in the last 180
days for greater than 7 days)

- Diabetes (defined by being on oral hypoglycemics or insulin)

- Psychiatric disorder such as severe depression, manic depressive disorder, obsessive
compulsive disorder or schizophrenia; (defined per medical history)

- Major surgery =< 28 days prior to registration

- Any of the following:

- Pregnant women

- Nursing women

- Women of childbearing potential who are unwilling to employ adequate
contraception

- Treatable causes of fatigue have not been ruled out, at least by history and exam
criteria, by the treating provider, such as uncontrolled pain, hypothyroidism, or
insomnia; NOTE: if these are considered to be the primary cause for the patient?s
fatigue then the patient is not eligible for this trial

- Patients with pain requiring opioid pain medication; NOTE: over the counter analgesics
such as Tylenol or ibuprofen are allowed

- New use of Ambien and/or other benzodiazepines =< 30 days prior to registration

- New use of sleep aids including melatonin =< 30 days prior to registration

- Use of full anticoagulant doses of coumadin or heparin (exception: 1 mg/day of
coumadin for preventing catheter clots is allowed)

- Use of monoamine oxidase inhibitors (MAOI) inhibitors

- Patients scoring greater than 4 on a 0 to 10 scale with regard to sleep troubles or
pain

- Patients planning to start any type of cancer therapy during the 8 week, double blind,
course of the study, once randomized on the study

- Patients with malnutrition, active infection, significant pulmonary disease and
cardiovascular disease as determined by the physician as they could impact fatigue

- Use of any over the counter herbal/dietary supplement marketed for fatigue or energy
(for example, products containing any type of ginseng, Rhodiola rosea, high doses of
caffeine, guarana, or anything called an ?adaptogen?)

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- History of myocardial infarction =< 180 days prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmia