A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma
- Conditions
- Soft Tissue Sarcoma
- Interventions
- Registration Number
- NCT01440088
- Lead Sponsor
- Threshold Pharmaceuticals
- Brief Summary
The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma.
- Detailed Description
TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Doxorubicin 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. Soft tissue sarcomas have evidence supporting the presence of hypoxia based on pO2 histography, F-MISO and gene expression profiling. There is an absence of therapeutic options for subjects with soft tissue sarcoma. Combining doxorubicin with TH-302 may enable the targeting of both the normoxic and hypoxic regions of soft tissue sarcoma.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 640
-
Male or female ≥ 15 years of age
-
Ability to understand the purposes and risks of the study and has signed or, if appropriate, the subject's parent or legal guardian has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
-
Pathologically confirmed diagnosis of soft tissue sarcoma of the following histopathologic types:
- Synovial sarcoma
- High grade fibrosarcoma
- Undifferentiated sarcoma; sarcoma not otherwise specified (NOS)
- Liposarcoma
- Leiomyosarcoma (excluding GIST)
- Angiosarcoma (excluding Kaposi's sarcoma)
- Malignant peripheral nerve sheath tumor
- Pleomorphic Rhabdomyosarcoma
- Myxofibrosarcoma
- Epithelioid sarcoma
- Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (MFH) (including pleomorphic, giant cell, myxoid and inflammatory forms)
-
Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate.
-
Recovered from reversible toxicities of prior therapy
-
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Life expectancy of at least 3 months
-
Acceptable liver, renal, hematological and cardiac function
-
All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception
- Prior systemic therapy for advanced or metastatic disease (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted). Palliative radiotherapy to non-target lesions is allowed if completed at least two weeks prior to study entry
- Low grade tumors according to standard grading systems
- Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards
- Prior therapy with an anthracycline or anthracenedione
- Prior mediastinal/cardiac radiotherapy
- Current use of drugs with known cardiotoxicity or known interactions with doxorubicin
- Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C). Palliative radiotherapy to non-target lesions is allowed, is completed at least two weeks prior to study entry.
- Significant cardiac dysfunction precluding treatment with doxorubicin
- Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last year
- Known brain metastases (unless previously treated and well controlled for a period of ≥ 3 months)
- Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
- Severe chronic obstructive or other pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Prior therapy with a hypoxic cytotoxin
- Subjects who participated in an investigational drug or device study within 28 days prior to study entry
- Known infection with HIV, hepatitis B, or hepatitis C
- Subjects who have exhibited allergic reactions to a structural compound similar to TH-302,doxorubicin or their excipients
- Females who are pregnant or breast-feeding
- Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- Unwillingness or inability to comply with the study protocol for any reason
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TH-302 in Combination with Doxorubicin TH-302 in Combination with Doxorubicin - Doxorubicin Doxorubicin -
- Primary Outcome Measures
Name Time Method Efficacy of TH-302 in combination with doxorubicin 2 years Efficacy will be determined by overall survival in subjects with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy compared with doxorubicin alone
- Secondary Outcome Measures
Name Time Method Safety of TH-302 in combination with doxorubicin in subjects with locally advanced unresectable or metastatic soft tissue sarcoma compared with doxorubicin alone 2 years To investigate the pharmacokinetics of TH-302, Br-IPM, doxorubicin, and doxorubicinol in plasma
Trial Locations
- Locations (92)
Oncology Specialists
🇺🇸Park Ridge, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Mayo Arizona
🇺🇸Scottsdale, Arizona, United States
USC-Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Columbia University Medical Center
🇺🇸NY, New York, United States
University of Pittsburg Medical Center
🇺🇸Pittsburg, Pennsylvania, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston Salem, North Carolina, United States
The Arthur G. James Cancer Hospital and Richard J Solove Research Institue, The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Cancer Care Manitoba
🇨🇦Winnipeg, Canada
Pennsylvania Oncology Hematology Associates
🇺🇸Philadelphia, Pennsylvania, United States
Dana Farber Cancer Institute Center for Sarcoma and Bone Oncology
🇺🇸Boston, Massachusetts, United States
Carolinas Hematology-oncology Associates-Blumenthal Cancer Center
🇺🇸Charlotte, North Carolina, United States
Juravinski Cancer Centre at Hamilton Health Sciences - Department of Medicine
🇨🇦Hamilton, Ontario, Canada
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Krankenhaus Nordwest GmbH
🇩🇪Frankfurt, Germany
South Florida Center for Gynecologic Oncology
🇺🇸Boca Raton, Florida, United States
Winship Cancer Institute of Emory University, Midtown Campus
🇺🇸Atlanta, Georgia, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
Mayo Clinic-Florida-Cancer Clinical Studies Unit
🇺🇸Jacksonville, Florida, United States
BCCA- Vancouver Cancer Centre - Division of Medical Oncology
🇨🇦Vancouver, Canada
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Stanford Comprehensive Cancer Center
🇺🇸Stanford, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Virginia Commonwealth Universtiy-Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University Klinikum Graz
🇦🇹Graz, Austria
Northwestern University
🇺🇸Chicago, Illinois, United States
Département d'Oncologie Moléculaire, Institut Paoli-Calmettes (IPC) and U119 Inserm
🇫🇷Marseille, France
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Centre Antoine Lacassagne
🇫🇷Nice, France
University of Iowa Health Care - University of Iowa Hospital
🇺🇸Iowa City, Iowa, United States
Mayo Rochester
🇺🇸Rochester, Minnesota, United States
Ottawa Health Research Institue
🇨🇦Ottawa, Canada
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Departement d'Oncologie Medicale
🇫🇷Dijon, France
University of Washington Cancer Center
🇺🇸Seattle, Washington, United States
CHU Strasbourg
🇫🇷Strasbourg, France
Centre Leon Berard
🇫🇷Lyon, France
Cross Cancer Institute
🇨🇦Edmonton, Canada
Wilhelm's University, Universitatsklinikum Muenster, Medizinische Klinik und Poliklinik A, Albert-Schweitzer-Campus 1
🇩🇪Munster, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
Sharette Institute of Oncology, Hadassah-Hebrew University Medical Center, Hadassah Medical Org-Ein Karem
🇮🇱Kiryat Hadassah, Jerusalem, Israel
ROTSN RAMS them. Н.Н.Блохина NN Blokhin
🇷🇺Moscow, Russian Federation
Div. of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center
🇩🇪Mannheim, Germany
Centrum Onkologii Instytut im M. Sklodowskiej-Curie
🇵🇱Krakow, Poland
Hospital Universitario Ramón y Cajal.
🇪🇸Madrid, Spain
GUZ "Regional Oncology Dispensay", Kazan
🇷🇺Kazan, Russian Federation
H.U. Canarias, Hospital Universitario de Canarias. Servicio de Oncología Médica
🇪🇸Tenerife, Canarias, Spain
Indiana University Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Allgemeines Krankenhaus Wien
🇦🇹Wien, Austria
Magyar Honvedseg Honvedkorhaz, Onkologiai Osztaly
🇭🇺Budapest, Hungary
Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Fondazione del Piemonte per l'Oncologia, Instituto per la Ricerca e la Cura del cancro (I.R.C.C.), Dipartimento Oncologico, Direzione Operativa Oncologia Medica a Direzione Universitaria
🇮🇹Candiolo, Torino, Italy
Centro di Riferimento Oncologico (CRO)
🇮🇹Aviano, Italy
Azienda Ospedaliera Garibaldi
🇮🇹Catania, Italy
Azienda Ospedaliero Universitaria-Policlinico Paolo Giacco
🇮🇹Palermo, Italy
ASL TO/2 di TORINO_Presidio Sanitario Gradenigo, S.C. di Oncologia
🇮🇹Torino, Italy
University Hospital Herlev at Copenhagen
🇩🇰Herlev, Copenhagen, Denmark
Washington Cancer Institute
🇺🇸Washington, District of Columbia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
H.Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
MD Anderson Cancer Center Orlando
🇺🇸Orlando, Florida, United States
Kootenai Health - Kootenai Cancer Center
🇺🇸Coeur d'Alene, Idaho, United States
Montefiore
🇺🇸Bronx, New York, United States
University Hospitals Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Canada
Institut Bergonie
🇫🇷Bordeaux, France
ICO Rene Gauducheau
🇫🇷Saint Herblain Cedex, Nantes, France
Institut Claudius Regaud
🇫🇷Toulouse Cedex, France
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Megyei Onkologiai Kozpont
🇭🇺Szolnok, Hungary
Hospital Sant Joan de Deu, Department de Oncologia
🇪🇸Barcelona, Spain
Universidad Complutense Madrid Facultad de Medicina - Hospital Universitario 12 de Octubre, Servicio de Oncologia Medica Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Institut Catala d'Oncologia
🇪🇸Barcelona, Spain
Medizinische Hochschule Hannover (MHH) - Klinik fuer Haemonstaseologie, Onkologie und Stammzelltransplantation
🇩🇪Hannover, Germany
Helios Klinikum Bad Saarow, Department of Hematology, Oncology, and Palliative Care, Sarcoma Center Berlin-Brandenburg
🇩🇪Berlin, Germany
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
MUSC - Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Univ. Klinik fur Innere Medizin I Internistische Onkologie Medizinische Universitat Innsbruck
🇦🇹Innsbruck, Austria
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
IRCCS Centro di Riferimento Oncologico-Struttura Operativa
🇮🇹Aviano, Pordenone, Italy
Wojewodzkie Centrum Onkologii
🇵🇱Gdansk, Poland
University of Vermont
🇺🇸Burlington, Vermont, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
FGU Moscow Research Institute of Oncology named after P.A. Hertzen of Rosmedtechnology
🇷🇺Moscow, Russian Federation