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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02093962
• Other study ID #: TH-CR-415
• Status: Terminated
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: May 2016

Study information

• Verified date: March 2021
• Source: Threshold Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 265
• Est. completion date: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• 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.
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Threshold Pharmaceuticals	EMD Serono

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Greece,  Hungary,  Italy,  Poland,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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