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Soft Tissue SarcomaPhase 3NCT01440088

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

A Phase 3 study testing TH-302 in Combination with Doxorubicin and Doxorubicin in people with Soft Tissue Sarcoma, run by Threshold Pharmaceuticals at 92 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
TH-302 in Combination with Doxorubicin and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
640 participants
Where
92 sitesin 13 countries
Study dates
Sep 2011to May 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
Show all 21Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

92 sites in 13 countries.

92 sites in 13 countries

United States44 sites

  • University of Michigan Cancer Center

    Ann Arbor, Michigan, 48109

  • Winship Cancer Institute of Emory University, Midtown Campus

    Atlanta, Georgia, 30322

  • Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • South Florida Center for Gynecologic Oncology

    Boca Raton, Florida, 33487

  • Dana Farber Cancer Institute Center for Sarcoma and Bone Oncology

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Vermont

    Burlington, Vermont, 05405

  • MUSC - Hollings Cancer Center

    Charleston, South Carolina, 29425

  • Carolinas Hematology-oncology Associates-Blumenthal Cancer Center

    Charlotte, North Carolina, 28203

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Kootenai Health - Kootenai Cancer Center

    Coeur d'Alene, Idaho, 83814

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

    Columbus, Ohio, 43202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Indiana University Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa Health Care - University of Iowa Hospital

    Iowa City, Iowa, 52242

  • Mayo Clinic-Florida-Cancer Clinical Studies Unit

    Jacksonville, Florida, 32224

  • USC-Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of California, Los Angeles

    Los Angeles, California, 90095-6901

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10031

  • Columbia University Medical Center

    New York, New York, 10032

  • MD Anderson Cancer Center Orlando

    Orlando, Florida, 32806

  • Oncology Specialists

    Park Ridge, Illinois, 60068

  • Pennsylvania Oncology Hematology Associates

    Philadelphia, Pennsylvania, 19106

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of Pittsburg Medical Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Virginia Commonwealth Universtiy-Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Rochester

    Rochester, Minnesota, 55905

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

  • Mayo Arizona

    Scottsdale, Arizona, 85259

  • University of Washington Cancer Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Comprehensive Cancer Center

    Stanford, California, 94305

  • H.Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Montefiore

    The Bronx, New York, 10461

  • Arizona Cancer Center

    Tucson, Arizona, 85719

  • Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Washington Cancer Institute

    Washington D.C., District of Columbia, 20010

  • Wake Forest University Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

France8 sites

  • Institut Bergonie

    Bordeaux, 33076

  • Departement d'Oncologie Medicale

    Dijon, 21079

  • Centre Leon Berard

    Lyon, 69008

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

    Marseille, 13009

  • Centre Antoine Lacassagne

    Nice

  • ICO Rene Gauducheau

    Saint-Herblain, Nantes, 44805

  • CHU Strasbourg

    Strasbourg, 67098

  • Institut Claudius Regaud

    Toulouse, 31052

Other trials in France

Canada7 sites

  • Tom Baker Cancer Centre

    Calgary, T2N4N2

  • Cross Cancer Institute

    Edmonton, T6G1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences - Department of Medicine

    Hamilton, Ontario, L8V5C2

  • McGill University Health Centre

    Montreal, Quebec, H3G 1A4

  • Ottawa Health Research Institue

    Ottawa, K1H8L6

  • BCCA- Vancouver Cancer Centre - Division of Medical Oncology

    Vancouver, V5Z4E6

  • Cancer Care Manitoba

    Winnipeg, R3E0V9

Other trials in Canada

Germany7 sites

  • HELIOS Klinikum Berlin-Buch

    Berlin, 13125

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

    Berlin, 15526

  • Universitätsklinikum Essen

    Essen, 45122

  • Krankenhaus Nordwest GmbH

    Frankfurt

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

    Hanover, 30625

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

    Mannheim, D-68165

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

    Münster, 48149

Other trials in Germany

Italy6 sites

  • IRCCS Centro di Riferimento Oncologico-Struttura Operativa

    Aviano, Pordenone, 33081

  • Centro di Riferimento Oncologico (CRO)

    Aviano, 33081

  • 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

  • Azienda Ospedaliera Garibaldi

    Catania, 95122

  • Azienda Ospedaliero Universitaria-Policlinico Paolo Giacco

    Palermo, 90127

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

    Torino, 10149

Other trials in Italy

Spain6 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Institut Catala d'Oncologia

    Barcelona, 08907

  • Hospital Sant Joan de Deu, Department de Oncologia

    Barcelona, 08950

  • Hospital Universitario Ramón y Cajal.

    Madrid, 28034

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

    Madrid, 28034

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

    Santa Cruz de Tenerife, Canary Islands, 38320

Other trials in Spain

Austria3 sites

  • University Klinikum Graz

    Graz, A-8036

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

    Innsbruck, A-6020

  • Allgemeines Krankenhaus Wien

    Vienna, A-1090

Other trials in Austria

Poland3 sites

  • Wojewodzkie Centrum Onkologii

    Gdansk, 80-219

  • Centrum Onkologii Instytut im M. Sklodowskiej-Curie

    Krakow, 31-115

  • Centrum Onkologii-Instytut im. M. Sklodowskiej-Curie

    Warsaw, 02-781

Other trials in Poland

Russia3 sites

  • GUZ "Regional Oncology Dispensay", Kazan

    Kazan', 420029

  • ROTSN RAMS them. Н.Н.Блохина NN Blokhin

    Moscow, 115478

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

    Moscow, 125284

Other trials in Russia

Hungary2 sites

  • Magyar Honvedseg Honvedkorhaz, Onkologiai Osztaly

    Budapest, H-1062

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

    Szolnok, H-5004

Other trials in Hungary

Belgium1 site

  • Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Denmark1 site

  • University Hospital Herlev at Copenhagen

    Herlev, Copenhagen, 2730

Other trials in Denmark

Israel1 site

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

    Kiryat Hadassah, Jerusalem, 91120

Other trials in Israel

About this study

Official title: A Randomized Phase 3, Multicenter, Open-Label Study Comparing TH-302 in Combination With Doxorubicin vs. Doxorubicin Alone in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

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.

Read the 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.

Being tested
TH-302 in Combination with Doxorubicin, Doxorubicin
Keywords
TH-302, TH-CR-406, SARC021, Locally Advanced Soft Tissue Sarcoma, Metastatic Soft Tissue Sarcoma, Sarcoma, Doxorubicin, Evofosfamide
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TH-302 in Combination with DoxorubicinDrug

    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.

  • DoxorubicinDrug

    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.

Study groups in NCT01440088
Study groupRoleWhat they receive
TH-302 in Combination with DoxorubicinExperimentalNot described
Receives: Drug: TH-302 in Combination with Doxorubicin
DoxorubicinActive comparatorNot described
Receives: Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 2 years

Secondary outcomes (1)

  1. Safety of TH-302 in combination with doxorubicin in subjects with locally advanced unresectable or metastatic soft tissue sarcoma compared with doxorubicin alone

    To investigate the pharmacokinetics of TH-302, Br-IPM, doxorubicin, and doxorubicinol in plasma

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionDec 2015
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
640 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01440088
Sponsor's protocol ID
TH-CR-406/SARC021
Status last verified
Jun 2016
First submitted
20 Sep 2011
Last updated
2 Jun 2016
Results posted
No
Data monitoring committee
Yes
Expanded access
Available

Publications

  • 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.

    PubMed 28651927

  • 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.

    PubMed 25185097

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TH-302 in Combination with Doxorubicin and Doxorubicin in people with Soft Tissue Sarcoma, run by Threshold Pharmaceuticals at 92 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States, France, Canada, Germany, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of TH-302 in combination with doxorubicin (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01440088, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2016.

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