A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer
Condition: Solid Tumor; Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Evofosfamide; Gemcitabine
Intervention description: Evofosfamide infusion intravenously at an escalated dose of 240, 340 or 480 milligram per square meter (mg/m^2) on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or withdrawal.; Gemcitabine 1000 mg/m^2 on Day 1, 8 and 15 of each 28-day treatment cycle until progressive disease, unacceptable toxicity or withdrawal.
Intervention MeSH terms: Gemcitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Solid tumor; Pancreatic cancer; TH-302; Gemcitabine; Evofosfamide

Summary:

      This is a Japanese Phase 1, open-label, and dose-escalating trial of TH-302 as monotherapy in
      subjects with solid tumors and in combination with gemcitabine in subjects with pancreatic
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 20 years of age

          -  Signed written informed consent form

          -  Histologically or cytologically confirmed advanced or metastatic solid tumor
             previously treated with one or more standard treatment regimen(s) or for which no
             effective therapy is available

          -  Histologically or cytologically confirmed locally advanced unresectable or metastatic
             pancreatic adenocarcinoma previously untreated with chemotherapy or systemic therapy

          -  Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy of at least 3 months

          -  Acceptable liver function, renal function, hematologic status and coagulation status
             as defined in the protocol

          -  No clinically significant abnormalities in urinalysis

          -  Effective contraception for both male and female subjects if the risk of conception
             exists

          -  Other inclusion criteria apply

        Exclusion Criteria:

          -  Prior anti-cancer treatment with more than 3 myelosuppressive cytotoxic chemotherapy
             regimens

          -  Prior treatment with gemcitabine for their advanced or metastatic pancreatic cancer,
             except for radiosensitizing doses of gemcitabine

          -  Prior radiotherapy to more than 30 percent of the bone marrow within 6 months prior to
             the trial entry

          -  Cardiac disease with New York Heart Association (NYHA) Class 3 or 4, within 6 months
             prior to the trial entry

          -  Clinically significant (that is, active) cardiovascular disease

          -  Seizure disorders requiring anticonvulsant therapy

          -  Known brain, leptomeningeal or epidural metastases (unless previously treated and well
             controlled for at least 3 months at the trial entry)

          -  Previously treated malignancies other than the current disease for at least 5 years at
             the trial entry

          -  Severe chronic obstructive or other pulmonary disease major surgery, within 4 weeks
             prior to the trial entry, without complete recovery

          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          -  Anti-cancer treatment prior to trial entry

          -  Participation in an investigational drug or device trial within 4 weeks prior to the
             trial entry

          -  Known infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C

          -  A history of allergic reactions

          -  Taking a medication that is either moderate or strong inhibitor or inducer of
             cytochrome P450 (CYP)3A4 or is a sensitive substrate of other cytochrome P450

          -  Pregnancy or lactation period

          -  Concomitant disease or condition that could interfere with the conduct of the trial,
             or that would, in the opinion of the Investigator, pose an unacceptable risk to the
             subject in this trial

          -  Unwillingness or inability to comply with the trial protocol for any reason

          -  Legal incapacity or limited legal capacity

          -  Other exclusion criteria apply