Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: TH-302 combination with pemetrexed; Matched placebo in combination with pemetrexed
Intervention description: 400 mg/m2 of TH-302 will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle.
Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after TH-302 administration.; Matched placebo will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle.
Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after placebo administration.
Intervention MeSH terms: Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 265.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TH-302; TH-CR-415; Pemetrexed; Non-small cell lung cancer; Lung cancer; Evofosfamide

Summary:

      The purpose of this study is to determine whether TH-302 in combination with pemetrexed is
      safe and effective in the treatment of non-squamous non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ≥ 18 years of age.

          -  Histologically or cytologically confirmed stage IIIB or IV NSCLC with non-squamous
             histology

          -  Recurrent or progressive disease after one prior platinum-based non-pemetrexed
             chemotherapy treatment for advanced disease with or without maintenance

          -  Neoadjuvant/adjuvant cytotoxic chemotherapy initiated < 12 months prior to study
             randomization will be counted as one prior treatment

          -  Neoadjuvant/adjuvant cytotoxic chemotherapy initiated ≥ 12 months prior to study
             randomization will not be counted as one prior chemotherapy treatment

          -  Use of targeted agents (e.g., monoclonal antibodies or kinase inhibitors) will not be
             counted as a prior chemotherapy treatment

          -  Patients with known EGFR-activating mutations or ALK rearrangements should have
             received treatment with a targeted kinase inhibitor (e.g., erlotinib, crizotinib) and
             no longer be considered as a candidate for such treatment

          -  Measurable disease according to RECIST 1.1

          -  ECOG performance status 0-1

          -  Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of
             prior therapy

          -  Adequate hematologic, hepatic, cardiac, and renal function

          -  Female patients of childbearing potential must have a negative serum or urine
             pregnancy test, whichever is considered standard by the institution

        Exclusion Criteria:

          -  Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or
             NSCLC NOS

          -  Prior therapy with pemetrexed

          -  Inability or unwillingness to take folic acid, vitamin B12 supplementation or
             corticosteroids

          -  Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long
             half-life) or for 2 days (short half-life, if CrCL <80 mL/min) before pemetrexed
             dosing and until 2 days after pemetrexed dosing

          -  Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the
             following criteria are met:

               -  brain metastases are stable and have been previously treated with either
                  whole-brain radiotherapy or gamma-knife surgery

               -  steroids are currently not required and more than 14 days since last steroid
                  treatment

          -  Symptomatic pleural effusion (> CTCAE Grade 1 dyspnea) that is not amenable to
             drainage

          -  Treatment with other systemic anticancer therapy within 4 weeks prior to the first
             dose of study medication

          -  Treatment with full field radiation therapy within 4 weeks or limited field radiation
             therapy within 2 weeks prior to the first dose of study medication

          -  Major surgery within 4 weeks or minor surgery within 2 weeks prior the first dose of
             study medication

          -  Elective or a planned major surgery while on study treatment

          -  Radiation therapy to greater than 25% of the bone marrow

          -  Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)

          -  Any other serious uncontrolled medical disorders or psychological conditions that may
             interfere with study conduct

          -  Concurrent active malignancy other than adequately treated basal cell or squamous cell
             carcinoma of the skin or pre-invasive carcinoma of the cervix.

          -  Pregnant or breast feeding

          -  Patients who are taking medications that prolong QT interval and have a risk of
             Torsades de Pointes (Appendix F) or who have a history of long QT syndrome

          -  Patients who are taking medications that are strong inducers or inhibitors of CYP3A4