Study of Minnelide™ in Patients With Advanced GI Tumors

This is a Phase 1, open label, multicenter, dose-escalation study of safety,
pharmacokinetics, and pharmacodynamics of Minnelide™

Minnelide™ will be given as a single agent intravenously as a 30-minute infusion daily x 21
days followed by a 7-day rest period. One cycle will equal 28 days. Dose escalation will
follow a modified Fibonacci design.

ELIGIBILITY CRITERIA:

Inclusion Criteria:

1. Histologically or cytologically confirmed gastrointestinal (GI) carcinoma, which has
progressed on standard therapies (surgery, radiotherapy, endocrine therapy,
chemotherapy), for which effective therapy is not available or for which patients are
not a candidate for or intolerant of such therapies.

2. Have one or more metastatic tumors measurable on CT scan or locally advanced
measurable disease that has clearly progressed after prior treatment per RECIST
criteria.

3. Male and female patients at least 18 years of age

4. Laboratory data as specified:

- Hematology: ANC >1500 cells/mm3, platelet count > 150,000 cells/mm3 and
Hemoglobin > 9 g/dL

- Hepatic: Direct bilirubin ≤1.5 X ULN; alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) ≤ 2.5 X ULN. For patients with known liver
metastases or liver neoplasms, then ALT or AST ≤ 5.0 X ULN is allowed

- Renal: serum creatinine WNL or calculated creatinine clearance ≥ 50
mL/min/1.73m2 for patients with creatinine levels above institutional normal

- Urinalysis: No clinically significant abnormalities

- Coagulation: INR within normal limits, PTT within normal limits

5. Estimated life expectancy of at least 3 months

6. Karnofsky Performance ≥ 70%

7. A negative serum pregnancy test (if female)

8. For men and women of child-producing potential - willingness to employ appropriate
contraceptive methods (including abstinence) during the study.

9. Ability to understand the requirements of the study, provide written informed consent
and authorization of use and disclosure of protected health information, and agree to
abide by the study restrictions and to return for the required assessments.

Exclusion Criteria:

1. Women who are pregnant or nursing. NOTE: Women of child-bearing potential and men
must agree to use adequate contraception (hormonal or barrier method of birth
control; or abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

2. New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.

3. Baseline QTc exceeding 450 msec (470 msec for females) using the Bazetts formula
and/or patients receiving class 1A or class III antiarrythmic agents.

4. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy.

5. Treatment with radiotherapy, chemotherapy or investigational therapy within 1 month
(or 5 half lifes for cytotoxics) prior to study entry (6 weeks for nitrosoureas or
Mitomycin C).

6. Known HIV, Hepatitis A, B or Hepatitis C infection

7. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor.

8. Participation in concurrent study of an investigational agent or device.

9. Unwillingness or inability to comply with procedures required in this protocol.

10. Any other condition including but not limited to major co-morbidities, which in the
opinion of the investigator would render the patient ineligible.