Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Drug: TH-302 combination with pemetrexedDrug: 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
- 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
-
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)
Research Medical Center
🇺🇸Kansas City, Kansas, United States
St. Joseph Mercy Ann Arbor Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Montefire-Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Department of Medical Oncology
🇬🇷Heraklion, Greece
California Cancer Center Associates
🇺🇸Fresno, California, United States
W.G. (Bill) Hefner VA Medical Center
🇺🇸Salisbury, North Carolina, United States
IASO General, Oncology Unit
🇬🇷Athens, Greece
Klinikum Frankfurt Höchst GmbH
🇩🇪Frankfurt, Germany
Regional Hospital T. Bta, Department of Pneumology
🇨🇿Zlin, Czechia
Koranyi National Institute of TBC and Pulmonology, 14th Dept of Pulmonology
🇭🇺Budapest, Hungary
Hospital Universitario La Fe, Servicio de Oncologia
🇪🇸Valencia, Spain
Thomayer Hospital, Clinic of Pneumology
🇨🇿Praha 4, Czechia
University General Hospital of Patras, Oncology Unit
🇬🇷Patras, Greece
Jimenez Diaz Foundation
🇪🇸Madrid, Spain
Asklepios Fachkliniken Munchen-Gaunting
🇩🇪Gauting, Bavaria, Germany
Marien Hospital Herne
🇩🇪Herne, North Rhine-Westphalia, Germany
City Clinical Oncology Center, Oncology Department (Thoracic Oncology)
🇷🇺St. Petersburg, Russian Federation
AMPM Research
🇺🇸Miami, Florida, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
IRCCS Azienda Ospedallera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genova, Italy
Maria Sklodowska-Curie Institute of Oncology in Warsaw
🇵🇱Warsaw, Poland
Blokhin Russian Oncology Research Center
🇷🇺Moscow, Russian Federation
Hetenyi Geza Hospital, Department of Oncology
🇭🇺Szolnok, Hungary
St. Petersburg Clinical Center for Applied Special Medical Services (Oncology)
🇷🇺St. Petersburg, Russian Federation
Prof. Dr. Ioan Chiricuta Institute of Oncology
🇷🇴Cluj-Napoca, Romania
Oncology Centre "Sf. Nectarie"
🇷🇴Craiova, Dolj County, Romania
Pro. Dr. Alex Trestioreanu Institute of Oncology
🇷🇴Bucharest, Romania
State Healthcare Institution: Nizhny Novgorod Regional Oncology Center
🇷🇺Nizhny Novgorod, Russian Federation
St. Petersburg 1st State Medical University n.a.I.P. Pavlov under the Ministry of Healthcare of the Russian Federation
🇷🇺St. Petersburg, Russian Federation
Universitatsklinikum Schleswig-Holstein
🇩🇪Lubeck, Germany
Lungen Clinic Grosshandsdorf GmbH
🇩🇪Grosshansdorf, Germany
Städtisches Klinikum München - Klinikum Bogenhausen
🇩🇪München, Germany
General University Hospital Gregorio Maranon, Dept. of Oncology
🇪🇸Madrid, Spain
University Hospital Virgen de Valme
🇪🇸Sevilla, Spain
VA Eastern Colorado Healthcare System
🇺🇸Denver, Colorado, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Clinical Research Alliance
🇺🇸New York, New York, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Ironwood Cancer and Research Centers
🇺🇸Chandler, Arizona, United States
UAB Cancer Center
🇺🇸Birmingham, Alabama, United States
UCLA-Department of Medicine a Division of Hem/Onc
🇺🇸Los Angeles, California, United States
California Cancer Center
🇺🇸Encinitas, California, United States
Cancer Specialists of North Florida - CBO
🇺🇸Jacksonville Beach, Florida, United States
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Ochsner Clinical Foundation
🇺🇸New Orleans, Louisiana, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
San Antonio Military Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Regional Cancer Care Institute at Regional Health
🇺🇸Rapid City, South Dakota, United States
Associates in Oncology & Hematology
🇺🇸Chattanooga, Tennessee, United States
General Univesity Hospital in Prague, Clinic of Oncology
🇨🇿Prague, Czechia
Fpr Belvoir Community Hospital
🇺🇸Fort Belvoir, Virginia, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Hospital Na Bulovce, Department of Pneumology and Thoracic Surgery
🇨🇿Liben, Czechia
Charité Universitätsmedizin Berlin;
🇩🇪Berlin, Germany
Universitätsklinikum Ulm; Zentrum für Innere Medizin
🇩🇪Ulm, Germany
Koranyi National Institute of TBC and Pulmonology, 6th Department of Pulmonology
🇭🇺Budapest, Hungary
Attikon University General Hospital
🇬🇷Athens, Greece
Csongrad County Hospital of Chest Diseases
🇭🇺Deszk, Hungary
"Mater Salutis" Hospital - Operative Unit of Oncology
🇮🇹Verona, Legnago, Italy
A.O.U.S. Luigi GonzagaUniversity Hospital
🇮🇹Orbassano, Torino, Italy
Koranyi National Institute of TBC and Pulmonology, 8th Department of Pulmonology
🇭🇺Budapest, Hungary
University of Debrecen, Medical and Health Science Center, Department of Pulmonology
🇭🇺Debrecen, Hungary
Hospital Bellaria "Carlo Alberto Pizzardi" - Operative Unit of Oncology
🇮🇹Bologna, Italy
European Institute of Oncology (IEO) - Medical Care Unit
🇮🇹Milan, Italy
S. Gerardo Hospital - Complex Structure of Medical Oncology
🇮🇹Monza, Italy
Azienda Ospedaliera Universitaria Policlinico della Seconda Universita di Napoli
🇮🇹Napoli, Italy
San Camillo-Forlanini Hospital - U.O.C. Pneumologia Oncologica 1
🇮🇹Rome, Italy
University Hospital of Pisa, Department of Cardothoracic Surgery, Operative unit of Pneumology
🇮🇹Pisa, Italy
L. Rydygier Provencial Hospitals in Torun, Dept. of Tumors Chemotherapy
🇵🇱Torun, Poland
Med-Polonia Sp. z o.o.
🇵🇱Poznan, Poland
"Santa Maria degli Angeli" - Hospital - Complex Operative Unit of Oncology
🇮🇹Pordenone, Italy
Republican Clinical Oncology Center under the Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Republic Of Tatarstan, Russian Federation
Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of Medical Sciences
🇷🇺Moscow, Russian Federation
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Dr. Peset University Hospital, Dept. of Oncology
🇪🇸Valencia, Spain
DORN VA Medical Center
🇺🇸Columbia, South Carolina, United States