A Phase II Biomarker Trial of Gelatin Encapsulated Extract of American Ginseng Root (LEAG) in Breast Cancer

Asian ginseng (Panax ginseng) and its close relative American ginseng (Panax quinquefolium)
are perennial aromatic herbs that are widely used in Asian medicine. Ginseng root is used as
a tonic thought to increase the body's resistance to stress and fatigue, to increase
endurance under heavy physical activity, and to improve well-being in age-related
debilitation. Most of the ginseng consumed, even in Asian populations, is American ginseng,
and the majority of American ginseng is grown and processed in Wisconsin, with quality and
standardization overseen by the Ginseng Board of Wisconsin. Furthermore, in Asian medicine,
Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium) are common
components in herbals used for cancer prevention and treatment. Indeed, retrospective studies
have shown that patients who consumed ginseng on a regular basis experienced cancers at a
reduced rate, however, breast cancer was not considered. Ginseng has been used medicinally
for over 2000 years and there are no substantiated serious adverse effects, and few, if any,
non-serious adverse effects. The World Health Organization lists ginseng as a traditional
medicine with very low toxicity. Clinical trials have also demonstrated an anti-hyperglycemic
action of American ginseng. These studies utilized capsules containing dried, ground
Ontario-grown P. qinquefolius L. root. The ground AG root preparation had an onset of action
of 40 minutes. They found no significant increase in anti-hyperglycemic action after 40
minutes and no significant increase in anti-hyperglycemic action using 1 gram versus 3 gram
dosing.

LEAG is a standardized preparation of lyophilized water-extract of American ginseng root in
250-mg gelatin capsules. The ginseng was purchased through the Ginseng Board of Wisconsin and
the lyophilized extract has been certified for percentage of each and total ginsenoside
content and screened for safe levels of minerals, metals, and pesticides by ConsumerLab.com,
a leading testing service company of dietary supplements.

Inclusion Criteria:

- Patients with cytologically confirmed breast cancer with biopsy showing invasive or
non-invasive (DCIS) at least 1.0 cm greatest diameter on imaging

- Surgical patients undergoing lumpectomy, subtotal or total mastectomy

- 18 years of age or greater

- female

- available tissue blocks from diagnostic biopsy

- negative pregnancy test, medical history of surgical sterilization, or 1 year post
menopausal

- must be willing to forego surgery for minimum of 5 days

- ability and willingness to sign written consent

- if hypertensive, on stable dose of medication at least 30 days

- if diabetic, well controlled (HbA1C < 8.5 within past 60 days or documented FPG < 140
mg/dl for 3 consecutive days

- ECOG status < 2 or Karnofsky of 60% or greater

Exclusion Criteria:

- previous or current malignancy, excluding non-melanomic skin cancer

- evidence of distant metastatic disease

- history of chemotherapy, biologic or radiotherapy with 6 months of biopsy

- usage of herbal supplements or alternative medications not approved by the FDA within
1 week of starting study drug. LEAG or related ginseng products, and combination
products containing ginseng, should be discontinued within 6 weeks of starting study
drug

- history of allergic reactions attributed to compounds of similar chemical or biologic
composition to LEAG

- history of chronic inflammatory process, including, but not limited to, rheumatoid
arthritis and lupus. This includes patients on concurrent systemic steroids or
anti-inflammatory medications

- active bleeding or a pathological condition that carries a high risk of bleeding

- any swallowing dysfunction

- uncontrolled intercurrent illness

- poorly controlled diabetes (control indicated with HbA1c < 8.5 within past 60 days or
documented fasting blood glucose < 140 mg/dl for three consecutive days)

- known diabetics who have experienced episodes of symptomatic hypoglycemia in the last
6 months are also considered poorly controlled and will be excluded from study
participation.

- uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHG)

- pregnant or breast feeding women Women must be willing to use birth control throughout
study duration.

- current investigational medications or treatment with an investigational agent within
6 weeks prior to biopsy

- current coumadin therapy or who have been treated with coumadin within the 2 weeks
prior to biopsy

- current monoamine oxidase inhibitors treatment