Clinical trial NCT02093962: Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: TH-302
TH-CR-415
Pemetrexed
Non-small cell lung cancer
Lung cancer
Evofosfamide
Lead sponsor: ImmunoGenesis
Sponsor class: INDUSTRY
Collaborators: name: EMD Serono
First posted: 2014-03-21
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Cancer Center
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Center
state: California
city: Fresno
country: United States
facility: California Cancer Center Associates
state: California
city: Los Angeles
country: United States
facility: UCLA-Department of Medicine a Division of Hem/Onc
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Healthcare System
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Jacksonville Beach
country: United States
facility: Cancer Specialists of North Florida - CBO
state: Florida
city: Miami
country: United States
facility: AMPM Research
state: Florida
city: Kansas City
country: United States
facility: Research Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinical Foundation
state: Louisiana
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Ann Arbor Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Bronx
country: United States
facility: Montefire-Einstein Center for Cancer Care
state: New York
city: New York
country: United States
facility: Clinical Research Alliance
state: New York
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Salisbury
country: United States
facility: W.G. (Bill) Hefner VA Medical Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Columbia
country: United States
facility: DORN VA Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Regional Cancer Care Institute at Regional Health
state: South Dakota
city: Chattanooga
country: United States
facility: Associates in Oncology & Hematology
state: Tennessee
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: Fort Belvoir
country: United States
facility: Fpr Belvoir Community Hospital
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Liben
country: Czechia
facility: Hospital Na Bulovce, Department of Pneumology and Thoracic Surgery
city: Prague
country: Czechia
facility: General Univesity Hospital in Prague, Clinic of Oncology
city: Praha 4
country: Czechia
facility: Thomayer Hospital, Clinic of Pneumology
city: Zlin
country: Czechia
facility: Regional Hospital T. Bta, Department of Pneumology
city: Gauting
country: Germany
facility: Asklepios Fachkliniken Munchen-Gaunting
state: Bavaria
city: Herne
country: Germany
facility: Marien Hospital Herne
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin;
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst GmbH
city: Grosshansdorf
country: Germany
facility: Lungen Clinic Grosshandsdorf GmbH
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Städtisches Klinikum München - Klinikum Bogenhausen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Zentrum für Innere Medizin
city: Athens
country: Greece
facility: IASO General, Oncology Unit
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Heraklion
country: Greece
facility: Department of Medical Oncology
city: Patras
country: Greece
facility: University General Hospital of Patras, Oncology Unit
city: Budapest
country: Hungary
facility: Koranyi National Institute of TBC and Pulmonology, 14th Dept of Pulmonology
city: Budapest
country: Hungary
facility: Koranyi National Institute of TBC and Pulmonology, 6th Department of Pulmonology
city: Budapest
country: Hungary
facility: Koranyi National Institute of TBC and Pulmonology, 8th Department of Pulmonology
city: Debrecen
country: Hungary
facility: University of Debrecen, Medical and Health Science Center, Department of Pulmonology
city: Deszk
country: Hungary
facility: Csongrad County Hospital of Chest Diseases
city: Szolnok
country: Hungary
facility: Hetenyi Geza Hospital, Department of Oncology
city: Verona
country: Italy
facility: "Mater Salutis" Hospital - Operative Unit of Oncology
state: Legnago
city: Orbassano
country: Italy
facility: A.O.U.S. Luigi GonzagaUniversity Hospital
state: Torino
city: Bologna
country: Italy
facility: Hospital Bellaria "Carlo Alberto Pizzardi" - Operative Unit of Oncology
city: Genova
country: Italy
facility: IRCCS Azienda Ospedallera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro
city: Milan
country: Italy
facility: European Institute of Oncology (IEO) - Medical Care Unit
city: Monza
country: Italy
facility: S. Gerardo Hospital - Complex Structure of Medical Oncology
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico della Seconda Universita di Napoli
city: Pisa
country: Italy
facility: University Hospital of Pisa, Department of Cardothoracic Surgery, Operative unit of Pneumology
city: Pordenone
country: Italy
facility: "Santa Maria degli Angeli" - Hospital - Complex Operative Unit of Oncology
city: Rome
country: Italy
facility: San Camillo-Forlanini Hospital - U.O.C. Pneumologia Oncologica 1
city: Poznan
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Torun
country: Poland
facility: L. Rydygier Provencial Hospitals in Torun, Dept. of Tumors Chemotherapy
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Institute of Oncology in Warsaw
city: Craiova
country: Romania
facility: Oncology Centre "Sf. Nectarie"
state: Dolj County
city: Bucharest
country: Romania
facility: Pro. Dr. Alex Trestioreanu Institute of Oncology
city: Cluj-Napoca
country: Romania
facility: Prof. Dr. Ioan Chiricuta Institute of Oncology
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Center under the Ministry of Healthcare of Tatarstan Republic
state: Republic Of Tatarstan
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of Medical Sciences
city: Moscow
country: Russian Federation
facility: Blokhin Russian Oncology Research Center
city: Nizhny Novgorod
country: Russian Federation
facility: State Healthcare Institution: Nizhny Novgorod Regional Oncology Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Clinical Center for Applied Special Medical Services (Oncology)
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg 1st State Medical University n.a.I.P. Pavlov under the Ministry of Healthcare of the Russian Federation
city: St. Petersburg
country: Russian Federation
facility: City Clinical Oncology Center, Oncology Department (Thoracic Oncology)
city: Madrid
country: Spain
facility: General University Hospital Gregorio Maranon, Dept. of Oncology
city: Madrid
country: Spain
facility: Jimenez Diaz Foundation
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Sevilla
country: Spain
facility: University Hospital Virgen de Valme
city: Valencia
country: Spain
facility: Dr. Peset University Hospital, Dept. of Oncology
city: Valencia
country: Spain
facility: Hospital Universitario La Fe, Servicio de Oncologia
Study officials:
affiliation: Threshold Pharmaceuticals
name: Tillman Pearce, MD
role: STUDY_CHAIR
affiliation: UCLA-Dept of Medicine a Div of Hem/Onc
name: Jonathan Goldman, MD
role: PRINCIPAL_INVESTIGATOR
References: