A Phase 1/2 Dose-Escalation Study of the Safety, Efficacy and Pharmacokinetics of Glufosfamide in Combination With Gemcitabine in Advanced Solid Tumors and Pancreatic Adenocarcinoma

Inclusion Criteria:

- At least 18 years of age

- Histologically or cytologically confirmed, locally advanced or metastatic solid
malignancy; previously treated with at least one chemotherapy regimen for advanced or
metastatic disease or no effective standard treatment is available OR

- Metastatic and/or locally advanced, inoperable pancreatic adenocarcinoma proven
either by histology (surgical biopsy) or cytology (CT- or endoscopic-guided)

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

- Recovered from reversible toxicities of prior therapy

- Karnofsky performance status ≥70

- Women of childbearing potential and men to use effective means of contraception from
entry into the study through 6 months after the last dose

- Ability to understand the purposes and risks of the study and provide written
informed consent.

Exclusion Criteria:

- Prior chemotherapy for metastatic/locally advanced pancreatic cancer

- Prior administration of gemcitabine

- Radiation therapy within 28 days prior to study start

- Hormonal therapy, biologic therapy, chemotherapy or other systemic anti-tumor therapy
for cancer within 21 days prior to study start

- Symptomatic brain metastases (baseline CT scan is not required in asymptomatic
subjects)

- Active, clinically significant infection requiring antibiotics

- Known HIV positive or active hepatitis B or C

- History or symptoms of cardiovascular disease (NYHA Class 3 or 4)

- Other primary malignancies (other than treated non-melanoma skin cancer or treated in
situ cancer) within the past 5 years

- Major surgery within 3 weeks of the start of study treatment, without complete
recovery

- Clinically significant abnormalities in laboratory test results (including complete
blood count, chemistry panel including electrolytes, and urinalysis)

- Hemoglobin <9 g/dL (may receive transfusion or erythropoietin to maintain),

- ANC <1500/μL,

- Platelet count <100,000/μL,

- Total bilirubin > 1.5 ×ULN,

- AST/ALT > 2.5-fold above ULN (>5-fold above ULN if liver metastases),

- Serum creatinine > 2 mg/dL,

- Creatinine clearance < 60 mL/min (calculated)

- Females who are pregnant or breast-feeding

- Participation in an investigational drug or device study within 28 days of the first
day of dosing on this study

- Concomitant disease or condition that could interfere with the conduct of the study

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