Advanced Non-Squamous, Non-Small Cell Lung Cancer MedDRA version: 18.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: TH-302
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NA
CAS Number: 918633-87-1
Current Sponsor code: TH-302
Other descriptive name: TH-302
Concentratio
Sponsors
Threshold Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women = 18 years of age. 2. Ability to understand the purposes and risks of the trial and has signed a written informed consent form approved by the investigator’s IRB/EC 3. Histologically or cytologically confirmed stage IIIB or IV (AJCC/UICC 7th edition) NSCLC with non-squamous histology (mixed histology allowed if all components are consistent with NSCLC) 4. Recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance a. Neoadjuvant/adjuvant cytotoxic chemotherapy initiated =65 years) yes F.1.3.1 Number of subjects for this age range 145
Exclusion criteria
Exclusion criteria: 1. Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or NSCLC NOS (not otherwise specified) 2. Prior therapy with pemetrexed 3. Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids 4.Inability of patients with mild to moderate renal insufficiency (creatinine clearance 45 to 79 mL/min) to discontinue non-steroidal anti-inflammatory drugs for 5 days (long half-life) or for 2 days before pemetrexed dosing and until 2 days after pemetrexed dosing. 5. Leptomeningial disease or any untreated or symptomatic brain metastases, unless the following criteria are met: a. Brain metastases are stable and have been previously treated with either whole-brain radiotherapy or gamma-knife surgery b. Steroids are currently not required and more than 14 days since last steroid treatment 6. Symptomatic pleural effusion (> CTCAE Grade 1 dyspnea) that is not amenable to drainage 7. Treatment with other systemic anticancer therapy within 4 weeks prior to the first dose of study medication 8. 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 9. Major surgery within 4 weeks or minor surgery within 2 weeks prior the first dose of study medication 10. Elective or a planned major surgery while on study treatment 11. Radiation therapy to greater than 25% of the bone marrow 12. Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)or prior vaccination against yellow fever. 13. Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct including but not limited to: clinically significant active infection (e.g., tuberculosis, viral hepatitis, HIV), recent (within 6 months) myocardial infarction or unstable angina, unstable arrhythmia, poorly-controlled hypertension or diabetes, or psychiatric condition or history of drug abuse that may interfere with the patient’s ability to follow study procedures 14. Patients with a previous malignancy within the past 3 years are excluded other than curatively treated basal cell or squamous cell carcinoma of the skin, early gastrointestinal or bladder cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC diagnosis. 15. Pregnant or breast feeding 16. 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 17. Patients who are taking medications that are strong inducers or inhibitors of CYP3A4 (Appendix E) 18. History of hypersensitivity reaction to any of the study treatment components, including polysorbate 80 19.Concurrent participation in another clinical trial or study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of pemetrexed in combination with TH-302 as determined by overall survival (OS) in patients with advanced non-squamous NSCLC in the second-line chemotherapy setting compared with pemetrexed in combination with placebo;Secondary Objective: 1. To assess the safety of pemetrexed in combination with TH-302 compared with pemetrexed in combination with placebo in this setting 2. To evaluate the anti-tumor activity of pemetrexed in combination with TH-302 as determined by progression-free survival (PFS) and response rate (RR) compared with pemetrexed in combination with placebo 3. To investigate the pharmacokinetics of TH-302 and Br-IPM in this patient population 4. To explore and compare quality of life and derive health state utilities as measured by the EQ-5D-5L and to compare time to symptomatic progression as measured by the Lung Cancer Symptom Scale (LCSS) in patients treated with pemetrexed in combination with TH-302 and pemetrexed in combination with placebo;Primary end point(s): The primary efficacy endpoint is overall survival.;Timepoint(s) of evaluation of this end point: Primary endpoint, overall survival (OS), is event based and will occur after 321 deaths. This is projected to occur approximately 15 months after the last patient is enrolled. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): RECIST 1.1 will be used to determine progression-free survival, objective tumor response, stable disease or better rate and duration of response.;Timepoint(s) of evaluation of this end point: Progression-free survival and overall response (secondary endpoints) data may mature sooner than OS data, however, both analyses will be performed with the same cut-off point as the OS data. | — |
Countries
Canada, Czech Republic, France, Germany, Greece, Hungary, Italy, Romania, Russian Federation, Spain, United States
Contacts
Public ContactLeslie Brand
Threshold Pharmaceuticals, Inc.
Outcome results
None listed