Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
Condition: Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: TH-302; Gemcitabine; Placebo (5 percent dextrose - D5W)
Intervention description: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.; Gemcitabine will be administered at a dose of 1000 (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.; TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Intervention MeSH terms: Gemcitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 693.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TH-302; Evofosfamide; Pancreatic Cancer; EMR200592-001

Summary:

      This Phase 3 trial is a randomized, double-blind, placebo-controlled trial of gemcitabine in
      combination with TH-302 compared to gemcitabine in combination with placebo in subjects with
      locally advanced unresectable or metastatic pancreatic adenocarcinoma. Randomized subjects
      will receive TH-302 plus gemcitabine or gemcitabine plus placebo in 4-week cycles until there
      is evidence of progressive disease, intolerable toxicity, or the subject discontinues from
      the trial for other reasons (for example, withdrawal of consent). The primary efficacy
      endpoint is overall survival (OS) time. The data cut-off for statistical analyses of the
      primary and secondary endpoints will be reached when 508 events (deaths) will be reported. No
      planned interim analyses will be conducted. An Independent Safety Monitoring Board (ISMB)
      will provide periodic evaluations of the unblinded safety data to ensure subject safety and
      the validity and scientific merit of the study. A total of 660 subjects will be enrolled.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age

          -  Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by
             histology or cytology and 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

          -  Measurable disease (at least one target lesion outside of previous radiation fields)
             or non-measurable disease by RECIST v.1.1 criteria

          -  Documentation of disease progression since any prior therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Life expectancy of at least 3 month

          -  Acceptable liver, renal function and acceptable hematological status

          -  Other protocol defined inclusion criteria may apply

        Exclusion Criteria:

          -  New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial
             infarction within 6 months prior to the date of randomization, unstable arrhythmia or
             symptomatic peripheral arterial vascular disease

          -  Symptomatic ischemic heart disease

          -  Known brain, leptomeningeal or epidural metastases (unless treated and well controlled
             for at least 3 months)

          -  Previous malignancy other than pancreatic cancer in the last 5 years, except for
             adequately treated non-melanoma skin cancer or pre-invasive cancer of the cervix

          -  Severe chronic obstructive or other pulmonary disease with hypoxemia

          -  Major surgery, other than diagnostic surgery, less than or equal to 28 days prior to
             the date of randomization. Subject must have completely recovered from surgery

          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          -  Treatment of pancreatic cancer with radiation therapy or surgery less than or equal to
             28 days prior to the date of randomization

          -  Prior therapy with a hypoxic cytotoxin

          -  Subjects who participated in an investigational drug or device trial less than or
             equal to 28 days prior to Day 1 of the first cycle

          -  Known infection with Human Immunodeficiency Virus (HIV), or an active infection with
             Hepatitis B or Hepatitis C

          -  Subjects who have exhibited allergic reactions to a structural compound similar to
             TH-302 or the drug product excipients or to gemcitabine or its excipients

          -  Other protocol defined exclusion criteria may apply