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

NCT02093962 | Terminated Phase 2 Results DMC

• 1 other identifier: TH-CR-415
• Study Type: interventional
• Target: 265
• Locations: 10 countries
• Sites: 80

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.

Conditions

Non-small Cell Lung Cancer

Keywords

TH-302; TH-CR-415; Pemetrexed; Non-small cell lung cancer; Lung cancer; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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

  2 years

Study Arms (2)

TH-302 and pemetrexed

EXPERIMENTAL

TH-302 in combination with pemetrexed

Drug: TH-302 combination with pemetrexed

Placebo and pemetrexed

ACTIVE COMPARATOR

Matching placebo in combination with pemetrexed

Drug: Matched placebo in combination with pemetrexed

Interventions

TH-302 combination with pemetrexed DRUG

400 mg/m2 of TH-302 will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after TH-302 administration.

TH-302 and pemetrexed

Matched placebo in combination with pemetrexed DRUG

Matched placebo will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after placebo administration.

Placebo and pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ImmunoGenesis: lead
• EMD Serono: collaborator

Study Sites (80)

UAB Cancer Center

Birmingham, Alabama, 35294, United States

Location

Ironwood Cancer and Research Centers

Chandler, Arizona, 85224, United States

Location

California Cancer Center

Encinitas, California, 92024, United States

Location

California Cancer Center Associates

Fresno, California, 93720, United States

Location

UCLA-Department of Medicine a Division of Hem/Onc

Los Angeles, California, 90095, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

VA Eastern Colorado Healthcare System

Denver, Colorado, 80220, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Cancer Specialists of North Florida - CBO

Jacksonville Beach, Florida, 32256, United States

Location

AMPM Research

Miami, Florida, 33133, United States

Location

Research Medical Center

Kansas City, Kansas, 64132, United States

Location

Ochsner Clinical Foundation

New Orleans, Louisiana, 70121, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

St. Joseph Mercy Ann Arbor Cancer Center

Ann Arbor, Michigan, 48106, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Clinical Research Alliance

New York, New York, 10021, United States

Location

Montefire-Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

Durham VA Medical Center

Durham, North Carolina, 27705, United States

Location

W.G. (Bill) Hefner VA Medical Center

Salisbury, North Carolina, 28144, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

DORN VA Medical Center

Columbia, South Carolina, 29209, United States

Location

Regional Cancer Care Institute at Regional Health

Rapid City, South Dakota, 57701, United States

Location

Associates in Oncology & Hematology

Chattanooga, Tennessee, 37421, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Oncology Consultants

Houston, Texas, 77024, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

Fpr Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Hospital Na Bulovce, Department of Pneumology and Thoracic Surgery

Libeň, 18081, Czechia

Location

General Univesity Hospital in Prague, Clinic of Oncology

Prague, 12800, Czechia

Location

Thomayer Hospital, Clinic of Pneumology

Prague, 140 59, Czechia

Location

Regional Hospital T. Bta, Department of Pneumology

Zlín, 76275, Czechia

Location

Asklepios Fachkliniken Munchen-Gaunting

Gauting, Bavaria, 82131, Germany

Location

Marien Hospital Herne

Herne, North Rhine-Westphalia, Germany

Location

Charité Universitätsmedizin Berlin;

Berlin, 12200, Germany

Location

Klinikum Frankfurt Höchst GmbH

Frankfurt, 65929, Germany

Location

Lungen Clinic Grosshandsdorf GmbH

Großhansdorf, 22927, Germany

Location

Universitatsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Städtisches Klinikum München - Klinikum Bogenhausen

München, 81925, Germany

Location

Universitätsklinikum Ulm; Zentrum für Innere Medizin

Ulm, 89081, Germany

Location

IASO General, Oncology Unit

Athens, 15562, Greece

Location

Attikon University General Hospital

Athens, Greece

Location

Department of Medical Oncology

Heraklion, 71110, Greece

Location

University General Hospital of Patras, Oncology Unit

Pátrai, 26500, Greece

Location

Koranyi National Institute of TBC and Pulmonology, 14th Dept of Pulmonology

Budapest, 1121, Hungary

Location

Koranyi National Institute of TBC and Pulmonology, 6th Department of Pulmonology

Budapest, 1121, Hungary

Location

Koranyi National Institute of TBC and Pulmonology, 8th Department of Pulmonology

Budapest, 1121, Hungary

Location

University of Debrecen, Medical and Health Science Center, Department of Pulmonology

Debrecen, 4032, Hungary

Location

Csongrad County Hospital of Chest Diseases

Deszk, 6772, Hungary

Location

Hetenyi Geza Hospital, Department of Oncology

Szolnok, 5004, Hungary

Location

"Mater Salutis" Hospital - Operative Unit of Oncology

Verona, Legnago, 37045, Italy

Location

A.O.U.S. Luigi GonzagaUniversity Hospital

Orbassano, Torino, 10043, Italy

Location

Hospital Bellaria "Carlo Alberto Pizzardi" - Operative Unit of Oncology

Bologna, 40139, Italy

Location

IRCCS Azienda Ospedallera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro

Genova, Italy

Location

European Institute of Oncology (IEO) - Medical Care Unit

Milan, 20141, Italy

Location

S. Gerardo Hospital - Complex Structure of Medical Oncology

Monza, 20900, Italy

Location

Azienda Ospedaliera Universitaria Policlinico della Seconda Universita di Napoli

Napoli, Italy

Location

University Hospital of Pisa, Department of Cardothoracic Surgery, Operative unit of Pneumology

Pisa, 56124, Italy

Location

"Santa Maria degli Angeli" - Hospital - Complex Operative Unit of Oncology

Pordenone, 33170, Italy

Location

San Camillo-Forlanini Hospital - U.O.C. Pneumologia Oncologica 1

Rome, 00152, Italy

Location

Med-Polonia Sp. z o.o.

Poznan, 60693, Poland

Location

L. Rydygier Provencial Hospitals in Torun, Dept. of Tumors Chemotherapy

Torun, 87-100, Poland

Location

Maria Sklodowska-Curie Institute of Oncology in Warsaw

Warsaw, 02781, Poland

Location

Oncology Centre "Sf. Nectarie"

Craiova, Dolj, Romania

Location

Pro. Dr. Alex Trestioreanu Institute of Oncology

Bucharest, 022328, Romania

Location

Prof. Dr. Ioan Chiricuta Institute of Oncology

Cluj-Napoca, 400015, Romania

Location

Republican Clinical Oncology Center under the Ministry of Healthcare of Tatarstan Republic

Kazan', Tatarstan Republic, 420029, Russia

Location

Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of Medical Sciences

Moscow, 115478, Russia

Location

Blokhin Russian Oncology Research Center

Moscow, 15478, Russia

Location

State Healthcare Institution: Nizhny Novgorod Regional Oncology Center

Nizhny Novgorod, 603081, Russia

Location

St. Petersburg Clinical Center for Applied Special Medical Services (Oncology)

Saint Petersburg, 194044, Russia

Location

St. Petersburg 1st State Medical University n.a.I.P. Pavlov under the Ministry of Healthcare of the Russian Federation

Saint Petersburg, 197101, Russia

Location

City Clinical Oncology Center, Oncology Department (Thoracic Oncology)

Saint Petersburg, 198255, Russia

Location

General University Hospital Gregorio Maranon, Dept. of Oncology

Madrid, 28007, Spain

Location

Jimenez Diaz Foundation

Madrid, 28040, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28222, Spain

Location

University Hospital Virgen de Valme

Seville, 41014, Spain

Location

Dr. Peset University Hospital, Dept. of Oncology

Valencia, 46017, Spain

Location

Hospital Universitario La Fe, Servicio de Oncologia

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Thomas Wilson
• Organization: Threshold Pharmaceuticals

twilson@thresholdpharm.com

302-359-0565

Study Officials

• Tillman Pearce, MD

  Threshold Pharmaceuticals

  STUDY CHAIR

• Jonathan Goldman, MD

  UCLA-Dept of Medicine a Div of Hem/Onc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 21, 2014
• Study Start: June 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 16, 2025
• Results First Posted: August 11, 2017

Record last verified: 2025-05

Locations

CZ (4); RO (3); DE (8); IT (10); ES (6); US (29); GR (4); RU (7); HU (6); PL (3)