Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma
Condition: Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Gemzar (Gemcitabine); TH-302; TH-302
Intervention description: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.; 240 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.; 340 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Intervention MeSH terms: Gemcitabine; Phosphoramide Mustards
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 214.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Locally Advanced Unresectable Pancreatic Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Summary:

      The purpose of this study is to determine whether Gemcitabine versus Gemcitabine and TH-302
      are effective in the treatment of subjects with first-line metastatic pancreatic
      adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. At least 18 years of age

          2. 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

          3. Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven
             either by histology or cytology previously untreated with chemotherapy or systemic
             therapy other than:

               -  Radiosensitizing doses of 5-fluorouracil;

               -  Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after
                  completion of gemcitabine;

               -  Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical
                  resection;

               -  Adjuvant chemotherapy if relapse occurred at least 6 months after completion of
                  adjuvant chemotherapy.

          4. Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of
             previous radiation fields)

          5. Documentation of disease progression since any prior therapy

          6. ECOG performance status of 0 or 1

          7. Life expectancy of at least 3 months

          8. Acceptable liver function:

               1. Bilirubin less than or equal to 1.5 times upper limit of normal

               2. AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times upper limit of normal
                  (ULN); if liver metastases are present, then less than or equal to 5 times ULN is
                  allowed

          9. Acceptable renal function:

             a. Serum creatinine less than or equal to ULN

         10. Acceptable hematologic status (without hematologic support):

               1. ANC greater than or equal to 1500 cells/μL

               2. Platelet count greater than or equal to 100,000/μL

               3. Hemoglobin greater than or equal to 9.0 g/dL

         11. All women of childbearing potential must have a negative serum pregnancy test and male
             and female 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:

          1. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial
             infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic
             peripheral arterial vascular disease

          2. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled
             for at least 3 months)

          3. Previously treated malignancies, except for adequately treated non-melanoma skin
             cancer, in situ cancer, or other cancer from which the subject has been disease-free
             for at least 5 years

          4. Severe chronic obstructive or other pulmonary disease with hypoxemia (requires
             supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse
             oximetry after a 2 minute walk) or in the opinion of the investigator any
             physiological state likely to cause systemic or regional hypoxemia

          5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without
             complete recovery

          6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          7. Treatment of pancreatic cancer with radiation therapy or surgery within 4 weeks prior
             to study entry

          8. Prior therapy with an hypoxic cytotoxin

          9. Subjects who participated in an investigational drug or device study within 28 days
             prior to study entry

         10. Known active infection with HIV, hepatitis B, or hepatitis

         11. Subjects who have exhibited allergic reactions to a structural compound, biological
             agent, or formulation (containing solutol and/or propylene glycol) similar to TH- 302

         12. Females who are pregnant or breast-feeding

         13. 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

         14. Unwillingness or inability to comply with the study protocol for any reason