A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Capsules Given Alone or in Combination With Protein-Bound Paclitaxel in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Patients with histologically confirmed advanced solid tumors (regimen A) or breast or
pancreas (regimen B)

- Tumor progression after receiving standard/approved chemotherapy or where there is no
approved therapy

- Prior treatment with protein-bound paclitaxel allowed if it has been six months since
received or progressed on protein-bound paclitaxel and plan to continue to receive
protein-bound paclitaxel with MinnelideTMcapsules

- One or more metastatic tumors measurable per RECIST Criteria

- Karnofsky performance ≥ 70%

- Life expectancy of at least 3 months

- Age: 18 years

- Signed, written IRB-approved informed consent

- A negative pregnancy test (if female)

- Acceptable liver function:

- Bilirubin 1.5 times upper limit of normal

- AST (SGOT), ALT (SGPT) and Alkaline phosphatase 2.5 times upper limit of normal
(if liver metastases are present, then 5 x ULN is allowed)

- Acceptable renal function:

o Serum creatinine within normal limits, OR calculated creatinine clearance 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

- Acceptable hematologic status:

- Granulocyte 1500 cells/mm3

- Platelet count 100,000 (plt/mm3)

- Hemoglobin 9 g/dL

- Urinalysis:

o No clinically significant abnormalities

- Acceptable coagulation status:

- PT ≤ 1.5 times institutional ULN

- PTT ≤ 1.5 times institutional ULN

- For men and women of child-producing potential, the use of effective contraceptive
methods during the study

Exclusion Criteria:

- 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

- Baseline QTc exceeding 450 msec (using the Bazett's formula) and/or patients receiving
class 1A or class III antiarrythmic agents.

- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy

- Pregnant or nursing women. 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.

- Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy
within one month prior to study entry (6 weeks for nitrosoureas or Mitomycin C).

- Unwillingness or inability to comply with procedures required in this protocol

- Known infection with HIV, hepatitis B, or hepatitis C

- 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

- Patients who are currently receiving any other investigational agent