Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer
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ClinicalTrials.gov Identifier: NCT02093962 |
Recruitment Status :
Terminated
(At the interim analysis, the futility boundary was not met and the study was stopped due to insufficient efficacy.)
First Posted : March 21, 2014
Results First Posted : August 11, 2017
Last Update Posted : September 25, 2017
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Condition or disease | Intervention/treatment | Phase |
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Non-small Cell Lung Cancer | Drug: TH-302 combination with pemetrexed Drug: Matched placebo in combination with pemetrexed | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 265 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Randomized Phase 2, Double-blind, Placebo-controlled, Multi-center Study Comparing Pemetrexed in Combination With TH-302 vs. Pemetrexed in Combination With Placebo as Second-line Chemotherapy for Advanced Non-Squamous, Non-Small Cell Lung Cancer |
Study Start Date : | June 2014 |
Actual Primary Completion Date : | April 2016 |
Actual Study Completion Date : | May 2016 |

Arm | Intervention/treatment |
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Experimental: TH-302 and pemetrexed
TH-302 in combination with pemetrexed
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Drug: TH-302 combination with pemetrexed
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. |
Active Comparator: Placebo and pemetrexed
Matching placebo in combination with pemetrexed
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Drug: Matched placebo in combination with pemetrexed
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. |
- Overall Survival [ Time Frame: 2 years ]To assess the efficacy of pemetrexed in combination with TH-302 as determined by overall survival in patients with advanced non-squamous NSCLC in the second-line chemotherapy setting compared with pemetrexed in combination with placebo

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02093962

Study Chair: | Tillman Pearce, MD | Threshold Pharmaceuticals | |
Principal Investigator: | Jonathan Goldman, MD | UCLA-Dept of Medicine a Div of Hem/Onc |
Responsible Party: | Threshold Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02093962 |
Other Study ID Numbers: |
TH-CR-415 |
First Posted: | March 21, 2014 Key Record Dates |
Results First Posted: | August 11, 2017 |
Last Update Posted: | September 25, 2017 |
Last Verified: | August 2017 |
TH-302 TH-CR-415 Pemetrexed |
Non-small cell lung cancer Lung cancer Evofosfamide |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Carcinoma, Bronchogenic Bronchial Neoplasms Pemetrexed Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |