Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer

• Status: Terminated
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Threshold Pharmaceuticals
• Collaborator: EMD Serono
• Treatments: Pemetrexed; Phosphoramide Mustards

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