Study of Safety and Efficacy of Glufosfamide in Combination With Gemcitabine in Cancer

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

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