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

Phase 2

Terminated

Conditions: Non-small Cell Lung Cancer

Interventions: Drug: TH-302 combination with pemetrexed
Drug: Matched placebo in combination with pemetrexed

Registration Number: NCT02093962

Lead Sponsor: ImmunoGenesis

Brief 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.

Detailed Description: TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Pemetrexed has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic microenvironment. There is evidence supporting the presence of hypoxia in NSCLC lesions based on a hypoxia PET study. Combining pemetrexed with TH-302 may enable the targeting of both the normoxic and hypoxic regions of NSCLC lesions.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 265

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TH-302 and pemetrexed	TH-302 combination with pemetrexed	TH-302 in combination with pemetrexed
Placebo and pemetrexed	Matched placebo in combination with pemetrexed	Matching placebo in combination with pemetrexed

Primary Outcome Measures

Name	Time	Method
Overall Survival	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

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (80): UAB Cancer Center
🇺🇸
Birmingham, Alabama, United States
Ironwood Cancer and Research Centers
🇺🇸
Chandler, Arizona, United States
California Cancer Center
🇺🇸
Encinitas, California, United States
California Cancer Center Associates
🇺🇸
Fresno, California, United States
UCLA-Department of Medicine a Division of Hem/Onc
🇺🇸
Los Angeles, California, United States
Sarcoma Oncology Research Center
🇺🇸
Santa Monica, California, United States
VA Eastern Colorado Healthcare System
🇺🇸
Denver, Colorado, United States
Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Cancer Specialists of North Florida - CBO
🇺🇸
Jacksonville Beach, Florida, United States
AMPM Research
🇺🇸
Miami, Florida, United States
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UAB Cancer Center
🇺🇸Birmingham, Alabama, United States