Trial of Mistletoe Extract in Patients With Advanced Solid Tumors

This study is a Phase I study that consists of two phases: a dose escalation phase and an
expansion phase. The dose escalation phase will be used to evaluate the safety and toxicity
of Helixor® M (mistletoe extract). An accelerated titration design (ATD) will be utilized to
determine the MTD. The expansion phase will be used to obtain preliminary efficacy data about
Helixor® M.

Any patients who have had any prior treatment with Mistletoe (injection or infusion) will
not be eligible for this study.

Inclusion Criteria:

1. Patients with advanced solid tumors who have had at least one line of FDA approved
therapy for metastatic disease (chemotherapy, immunotherapy, hormonal therapy or other
standard treatment). Patients must either have progressed, are refractory, have stable
disease and/or removed from therapy due to toxicities

2. Have measurable disease

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

4. Adequate organ function as defined by study-specified laboratory tests

5. Must use acceptable form of birth control through the study and for 28 days after
final dose of study drug

6. Signed informed consent form

7. Willing and able to comply with study procedures

Exclusion Criteria:

1. Patient with a known history or evidence of brain metastases

2. Patient who has had chemotherapy, radiation, hormonal, or biological cancer therapy
within 28 days prior to the first dose of study drug

3. Patient is currently participating or has participated in a study of an
investigational agent or using an investigational device within 28 days of the first
dose of study drug

4. Patients who have had surgery within 28 days of dosing of investigational agent,
excluding minor procedures (dental work, skin biopsy, etc), celiac plexus block, and
biliary stent placement

5. Patient is expected to require any other form of systemic or localized antineoplastic
therapy while on study

6. Patient who has had any prior treatment with Mistletoe (injection or infusion)

7. Patients who have received systemic corticosteroids within 28 days prior to the first
dose of study drug

8. Patients who have received systemic NSAID therapy within 14 days prior to the first
dose of study drug

9. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Mistletoe

10. 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

11. Autoimmune disease: Patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor
neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and
Myasthenia Gravis, multiple sclerosis). History of Grave's disease on stable thyroid
hormone replacement for at least 1 year is allowed

12. Patients with a known history of HIV, hepatitis B, hepatitis C, or tuberculosis
infection. Patients with a history of cleared hepatitis C (undetectable viral loads)
are allowed.

13. Women with a positive pregnancy test on enrollment or prior to investigational product
administration

14. Women who are pregnant or breastfeeding

15. Sexually active fertile men not using effective birth control if their partners are of
child bearing potential

16. Patient is unwilling or unable to comply with study procedures and/ or schedule.