The purpose of this study is to determine the safety of glufosfamide when administered in combination with gemcitabine.

This study, TH-CR-301, is a Phase 1/2 study that will evaluate the efficacy and safety of glufosfamide in combination with gemcitabine in advanced solid tumors or in first line treatment of pancreatic cancer.

Study Hypothesis: Glufosfamide in combination with gemcitabine may provide benefits in survival to patients with advanced solid tumors or metastatic pancreatic cancer.

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