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

Phase 1

Conditions: Advanced Non-Squamous, Non-Small Cell Lung Cancer
MedDRA version: 18.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-004698-29-CZ

Lead Sponsor: Threshold Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 440

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 < 12 months prior to study randomization will be counted as one prior treatment
b. Neoadjuvant/adjuvant cytotoxic chemotherapy initiated = 12 months prior to study randomization will not be counted as one prior chemotherapy treatment
c. Use of targeted agents (e.g., monoclonal antibodies or kinase inhibitors) will not be counted as a prior chemotherapy treatment
5. 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
6. Measurable disease according to RECIST 1.1
7. ECOG performance status 0-1
8. Life expectancy of = 3 months
9. Resolution to Grade = 1 Adverse Events, of all clinically significant toxic effects of prior therapy (e.g. radiation therapy, maintenance therapy, biopsy procedure; surgery)
10. Adequate hematologic, hepatic, and renal function
a. Hemoglobin =10 g/dl
b. Neutrophils =1,500/mm3 (not requiring G-CSF support)
c. Platelets = 100,000/mm3
d. Bilirubin <1.5 x ULN (except for patients with Gilbert syndrome)
e. AST and/or /ALT = 5 ULN
f. Creatinine clearance = 45mL/min (Cockcroft-Gault)
11. QTc interval of = 450 msec (males) or 470 msec (females) calculated according to Fridericia’s formula (QTc = QT/RR0.33; RR=RR interval)
12. If the patient has reproductive potential, must either be postmenopausal for more than 1 year, surgically sterile, or using effective contraception and agrees to use double barrier or hormonal contraception during the study period and for up to 6 months after the last dose of study medication
13. Female patients of childbearing potential must have a negative serum or urine pregnancy test, whichever is considered standard by the institution.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 295
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 145

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 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
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)
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. Concurrent active malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A patient with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for = 3 years
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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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