A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

NCT01440088 | Completed Phase 3 DMC

• 1 other identifier: TH-CR-406/SARC021
• Study Type: interventional
• Target: 640
• Locations: 13 countries
• Sites: 92

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.

Conditions

Soft Tissue Sarcoma

Keywords

TH-302; TH-CR-406; SARC021; Locally Advanced Soft Tissue Sarcoma; Metastatic Soft Tissue Sarcoma; Sarcoma; Doxorubicin; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• Efficacy of TH-302 in combination with doxorubicin

  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

  2 years

Secondary Outcomes (1)

• 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

Study Arms (2)

TH-302 in Combination with Doxorubicin

EXPERIMENTAL

Drug: TH-302 in Combination with Doxorubicin

Doxorubicin

ACTIVE COMPARATOR

Drug: Doxorubicin

Interventions

TH-302 in Combination with Doxorubicin DRUG

300 mg/m2 of TH-302 will be administered by IV infusion over 30-60 minutes on Days 1 and 8 of a 21-day cycle. Doxorubicin may be delivered as a bolus administration or as a continuous infusion administration; administration schedule must be specified prior to enrollment. Doxorubicin bolus administration: 75 mg/m2 administered by bolus injection starting on Day 1 of a 21-day cycle. Doxorubicin continuous administration: 75 mg/m2 administered by continuous IV infusion over 48-96 hours starting on Day 1 of a 21-day cycle. Doxorubicin administration will start between 2 to 4 hours after completion of the TH-302 infusion when used in combination with TH-302.

TH-302 in Combination with Doxorubicin

Doxorubicin DRUG

Doxorubicin may be delivered as a bolus administration or as a continuous infusion administration; administration schedule must be specified prior to enrollment. Doxorubicin bolus administration: 75 mg/m2 administered by bolus injection starting on Day 1 of a 21-day cycle. Doxorubicin continuous administration: 75 mg/m2 administered by continuous IV infusion over 48-96 hours starting on Day 1 of a 21-day cycle.

Doxorubicin

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead
• Sarcoma Alliance for Research through Collaboration (SARC): collaborator

Study Sites (92)

Mayo Arizona

Scottsdale, Arizona, 85259, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

USC-Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095-6901, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Washington Cancer Institute

Washington D.C., District of Columbia, 20010, United States

Location

South Florida Center for Gynecologic Oncology

Boca Raton, Florida, 33487, United States

Location

Mayo Clinic-Florida-Cancer Clinical Studies Unit

Jacksonville, Florida, 32224, United States

Location

MD Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

H.Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University, Midtown Campus

Atlanta, Georgia, 30322, United States

Location

Kootenai Health - Kootenai Cancer Center

Coeur d'Alene, Idaho, 83814, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Oncology Specialists

Park Ridge, Illinois, 60068, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Health Care - University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute Center for Sarcoma and Bone Oncology

Boston, Massachusetts, 02215, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10031, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore

The Bronx, New York, 10461, United States

Location

Carolinas Hematology-oncology Associates-Blumenthal Cancer Center

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Arthur G. James Cancer Hospital and Richard J Solove Research Institue, The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MUSC - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Vermont

Burlington, Vermont, 05405, United States

Location

Virginia Commonwealth Universtiy-Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

University of Washington Cancer Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University Klinikum Graz

Graz, A-8036, Austria

Location

Univ. Klinik fur Innere Medizin I Internistische Onkologie Medizinische Universitat Innsbruck

Innsbruck, A-6020, Austria

Location

Allgemeines Krankenhaus Wien

Vienna, A-1090, Austria

Location

Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg

Leuven, 3000, Belgium

Location

Juravinski Cancer Centre at Hamilton Health Sciences - Department of Medicine

Hamilton, Ontario, L8V5C2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

Location

Tom Baker Cancer Centre

Calgary, T2N4N2, Canada

Location

Cross Cancer Institute

Edmonton, T6G1Z2, Canada

Location

Ottawa Health Research Institue

Ottawa, K1H8L6, Canada

Location

BCCA- Vancouver Cancer Centre - Division of Medical Oncology

Vancouver, V5Z4E6, Canada

Location

Cancer Care Manitoba

Winnipeg, R3E0V9, Canada

Location

University Hospital Herlev at Copenhagen

Herlev, Copenhagen, 2730, Denmark

Location

ICO Rene Gauducheau

Saint-Herblain, Nantes, 44805, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Departement d'Oncologie Medicale

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Département d'Oncologie Moléculaire, Institut Paoli-Calmettes (IPC) and U119 Inserm

Marseille, 13009, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CHU Strasbourg

Strasbourg, 67098, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Helios Klinikum Bad Saarow, Department of Hematology, Oncology, and Palliative Care, Sarcoma Center Berlin-Brandenburg

Berlin, 15526, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, Germany

Location

Medizinische Hochschule Hannover (MHH) - Klinik fuer Haemonstaseologie, Onkologie und Stammzelltransplantation

Hanover, 30625, Germany

Location

Div. of Surgical Oncology & Thoracic Surgery, Mannheim University Medical Center

Mannheim, D-68165, Germany

Location

Wilhelm's University, Universitatsklinikum Muenster, Medizinische Klinik und Poliklinik A, Albert-Schweitzer-Campus 1

Münster, 48149, Germany

Location

Magyar Honvedseg Honvedkorhaz, Onkologiai Osztaly

Budapest, H-1062, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Megyei Onkologiai Kozpont

Szolnok, H-5004, Hungary

Location

Sharette Institute of Oncology, Hadassah-Hebrew University Medical Center, Hadassah Medical Org-Ein Karem

Kiryat Hadassah, Jerusalem, 91120, Israel

Location

IRCCS Centro di Riferimento Oncologico-Struttura Operativa

Aviano, Pordenone, 33081, Italy

Location

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, 10060, Italy

Location

Centro di Riferimento Oncologico (CRO)

Aviano, 33081, Italy

Location

Azienda Ospedaliera Garibaldi

Catania, 95122, Italy

Location

Azienda Ospedaliero Universitaria-Policlinico Paolo Giacco

Palermo, 90127, Italy

Location

ASL TO/2 di TORINO_Presidio Sanitario Gradenigo, S.C. di Oncologia

Torino, 10149, Italy

Location

Wojewodzkie Centrum Onkologii

Gdansk, 80-219, Poland

Location

Centrum Onkologii Instytut im M. Sklodowskiej-Curie

Krakow, 31-115, Poland

Location

Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

GUZ "Regional Oncology Dispensay", Kazan

Kazan', 420029, Russia

Location

ROTSN RAMS them. Н.Н.Блохина NN Blokhin

Moscow, 115478, Russia

Location

FGU Moscow Research Institute of Oncology named after P.A. Hertzen of Rosmedtechnology

Moscow, 125284, Russia

Location

H.U. Canarias, Hospital Universitario de Canarias. Servicio de Oncología Médica

Santa Cruz de Tenerife, Canary Islands, 38320, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Institut Catala d'Oncologia

Barcelona, 08907, Spain

Location

Hospital Sant Joan de Deu, Department de Oncologia

Barcelona, 08950, Spain

Location

Hospital Universitario Ramón y Cajal.

Madrid, 28034, Spain

Location

Universidad Complutense Madrid Facultad de Medicina - Hospital Universitario 12 de Octubre, Servicio de Oncologia Medica Hospital Universitario 12 de Octubre

Madrid, 28034, Spain

Location

Related Publications (2)

• Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schoffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. doi: 10.1016/S1470-2045(17)30381-9. Epub 2017 Jun 23.

  PMID: 28651927 DERIVED

• Chawla SP, Cranmer LD, Van Tine BA, Reed DR, Okuno SH, Butrynski JE, Adkins DR, Hendifar AE, Kroll S, Ganjoo KN. Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. J Clin Oncol. 2014 Oct 10;32(29):3299-306. doi: 10.1200/JCO.2013.54.3660. Epub 2014 Sep 2.

  PMID: 25185097 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

TH 302; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• William Tap, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: September 26, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: June 2, 2016

Record last verified: 2016-06

Locations

DE (7); DK (1); PL (3); ES (6); US (44); IL (1); RU (3); BE (1); CA (7); HU (2); IT (6); FR (8); AU (3)