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

NCT ID: NCT02093962

Last Updated: 2025-05-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

265 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2016-05-31

Brief Summary

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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

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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.

Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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TH-302 and pemetrexed

TH-302 in combination with pemetrexed

Group Type EXPERIMENTAL

TH-302 combination with pemetrexed

Intervention Type 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.

Placebo and pemetrexed

Matching placebo in combination with pemetrexed

Group Type ACTIVE_COMPARATOR

Matched placebo in combination with pemetrexed

Intervention Type 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.

Interventions

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TH-302 combination with pemetrexed

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.

Intervention Type DRUG

Matched placebo in combination with pemetrexed

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EMD Serono

INDUSTRY

Sponsor Role collaborator

ImmunoGenesis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tillman Pearce, MD

Role: STUDY_CHAIR

Threshold Pharmaceuticals

Jonathan Goldman, MD

Role: PRINCIPAL_INVESTIGATOR

UCLA-Dept of Medicine a Div of Hem/Onc

Locations

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UAB Cancer Center

Birmingham, Alabama, United States

Site Status

Ironwood Cancer and Research Centers

Chandler, Arizona, United States

Site Status

California Cancer Center

Encinitas, California, United States

Site Status

California Cancer Center Associates

Fresno, California, United States

Site Status

UCLA-Department of Medicine a Division of Hem/Onc

Los Angeles, California, United States

Site Status

Sarcoma Oncology Research Center

Santa Monica, California, United States

Site Status

VA Eastern Colorado Healthcare System

Denver, Colorado, United States

Site Status

Christiana Care Health Services

Newark, Delaware, United States

Site Status

Cancer Specialists of North Florida - CBO

Jacksonville Beach, Florida, United States

Site Status

AMPM Research

Miami, Florida, United States

Site Status

Research Medical Center

Kansas City, Kansas, United States

Site Status

Ochsner Clinical Foundation

New Orleans, Louisiana, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

St. Joseph Mercy Ann Arbor Cancer Center

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Clinical Research Alliance

New York, New York, United States

Site Status

Montefire-Einstein Center for Cancer Care

The Bronx, New York, United States

Site Status

Durham VA Medical Center

Durham, North Carolina, United States

Site Status

W.G. (Bill) Hefner VA Medical Center

Salisbury, North Carolina, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

DORN VA Medical Center

Columbia, South Carolina, United States

Site Status

Regional Cancer Care Institute at Regional Health

Rapid City, South Dakota, United States

Site Status

Associates in Oncology & Hematology

Chattanooga, Tennessee, United States

Site Status

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Site Status

Oncology Consultants

Houston, Texas, United States

Site Status

Millennium Oncology

Houston, Texas, United States

Site Status

Fpr Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Hospital Na Bulovce, Department of Pneumology and Thoracic Surgery

Libeň, , Czechia

Site Status

General Univesity Hospital in Prague, Clinic of Oncology

Prague, , Czechia

Site Status

Thomayer Hospital, Clinic of Pneumology

Prague, , Czechia

Site Status

Regional Hospital T. Bta, Department of Pneumology

Zlín, , Czechia

Site Status

Asklepios Fachkliniken Munchen-Gaunting

Gauting, Bavaria, Germany

Site Status

Marien Hospital Herne

Herne, North Rhine-Westphalia, Germany

Site Status

Charité Universitätsmedizin Berlin;

Berlin, , Germany

Site Status

Klinikum Frankfurt Höchst GmbH

Frankfurt, , Germany

Site Status

Lungen Clinic Grosshandsdorf GmbH

Großhansdorf, , Germany

Site Status

Universitatsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status

Städtisches Klinikum München - Klinikum Bogenhausen

München, , Germany

Site Status

Universitätsklinikum Ulm; Zentrum für Innere Medizin

Ulm, , Germany

Site Status

IASO General, Oncology Unit

Athens, , Greece

Site Status

Attikon University General Hospital

Athens, , Greece

Site Status

Department of Medical Oncology

Heraklion, , Greece

Site Status

University General Hospital of Patras, Oncology Unit

Pátrai, , Greece

Site Status

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

Budapest, , Hungary

Site Status

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

Budapest, , Hungary

Site Status

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

Budapest, , Hungary

Site Status

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

Debrecen, , Hungary

Site Status

Csongrad County Hospital of Chest Diseases

Deszk, , Hungary

Site Status

Hetenyi Geza Hospital, Department of Oncology

Szolnok, , Hungary

Site Status

"Mater Salutis" Hospital - Operative Unit of Oncology

Verona, Legnago, Italy

Site Status

A.O.U.S. Luigi GonzagaUniversity Hospital

Orbassano, Torino, Italy

Site Status

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

Bologna, , Italy

Site Status

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

Genova, , Italy

Site Status

European Institute of Oncology (IEO) - Medical Care Unit

Milan, , Italy

Site Status

S. Gerardo Hospital - Complex Structure of Medical Oncology

Monza, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico della Seconda Universita di Napoli

Napoli, , Italy

Site Status

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

Pisa, , Italy

Site Status

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

Pordenone, , Italy

Site Status

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

Rome, , Italy

Site Status

Med-Polonia Sp. z o.o.

Poznan, , Poland

Site Status

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

Torun, , Poland

Site Status

Maria Sklodowska-Curie Institute of Oncology in Warsaw

Warsaw, , Poland

Site Status

Oncology Centre "Sf. Nectarie"

Craiova, Dolj, Romania

Site Status

Pro. Dr. Alex Trestioreanu Institute of Oncology

Bucharest, , Romania

Site Status

Prof. Dr. Ioan Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Site Status

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

Kazan', Tatarstan Republic, Russia

Site Status

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

Moscow, , Russia

Site Status

Blokhin Russian Oncology Research Center

Moscow, , Russia

Site Status

State Healthcare Institution: Nizhny Novgorod Regional Oncology Center

Nizhny Novgorod, , Russia

Site Status

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

Saint Petersburg, , Russia

Site Status

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

Saint Petersburg, , Russia

Site Status

City Clinical Oncology Center, Oncology Department (Thoracic Oncology)

Saint Petersburg, , Russia

Site Status

General University Hospital Gregorio Maranon, Dept. of Oncology

Madrid, , Spain

Site Status

Jimenez Diaz Foundation

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Site Status

University Hospital Virgen de Valme

Seville, , Spain

Site Status

Dr. Peset University Hospital, Dept. of Oncology

Valencia, , Spain

Site Status

Hospital Universitario La Fe, Servicio de Oncologia

Valencia, , Spain

Site Status

Countries

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United States Czechia Germany Greece Hungary Italy Poland Romania Russia Spain

Other Identifiers

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TH-CR-415

Identifier Type: -

Identifier Source: org_study_id

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