A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors

Inclusion Criteria:

- At least 18 years of age

- Ability to understand the purposes and risks of the study and has signed a written
informed consent form approved by the investigator's IRB/Ethics Committee

- Histologically or cytologically confirmed advanced or metastatic solid malignancy

- Advanced or metastatic solid malignancy previously treated with one or more regimens
of chemotherapy or for which no effective therapy is available

- Recovered from toxicities of prior therapy

- Measurable disease by RECIST criteria (at least one target lesion)

- ECOG performance status of 0 or 1

- Life expectancy of at least 3 months

- Acceptable liver function:

- Bilirubin ≤ 1.5 times upper limit of normal

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

- Acceptable renal function:

- Serum creatinine ≤ ULN

- Acceptable hematologic status (without hematologic support):

- ANC ≥ 1500 cells/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 9.0 g/dL

- Urinalysis: No clinically significant abnormalities

- Acceptable coagulation status:

- PT ≤ 1.3 x ULN

- PTT ≤ 1.3 x ULN

- All women of childbearing potential must have a negative serum pregnancy test and
women and men subjects must agree to use effective means of contraception (surgical
sterilization or the use or barrier contraception with either a condom or diaphragm in
conjunction with spermicidal gel or an IUD) with their partner from entry into the
study through 6 months after the last dose

Exclusion Criteria:

- Prior treatment with high dose chemotherapy

- Prior radiotherapy to more than 25% of the bone marrow

- New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial
infarction within 6 months prior to Day 1, or unstable arrhythmia

- Seizure disorders requiring anticonvulsant therapy

- Symptomatic brain metastases (unless previously treated and well controlled for a
period of ≥ 3 months)

- Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the
investigator any physiological state leading to hypoxemia

- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without
complete recovery

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

- Treatment with radiation therapy, surgery, chemotherapy, targeted therapies
(erlotinib, lapatinib, etc.) or hormones within 4 weeks prior to study entry (6 weeks
for nitrosoureas or Mitomycin C)

- Patients who participated in an investigational drug or device study within 28 days
prior to study entry

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

- Patients who have exhibited allergic reactions to a similar structural compound,
biological agent, or formulation (containing solutol and/or propylene glycol)

- Females who are pregnant or breast-feeding

- Concomitant disease or condition that could interfere with the conduct of the study,
or that would, in the opinion of the investigator, pose an unacceptable risk to the
subject in this study

- Unwillingness or inability to comply with the study protocol for any reason