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NCT04031677PHASE3Recruiting

Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma

European Organisation for Research and Treatment of Cancer - EORTC

Start Date

1/20/2021

Completion Date

4/21/2028

Summary

This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.

Detailed Description

Standard arm: * Large en-bloc curative-intent surgery within 4 weeks following randomization- Experimental arm Experimental arm: * 3 cycles of neoadjuvant chemotherapy starting within 2 weeks following randomization: * High grade LPS: ADM (doxorubicin) 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m3 Q3 weeks. * LMS: ADM 75 mg/m2 + DTIC (dacarbazine) 1 g/m2 Q3 weeks * re-assessment of operability * curative-intent surgery within 3-6 weeks of last cycle of chemotherapy

Eligibility Criteria

Age Range: 18 years to No maximum

1. STRASS 2 Inclusion Criteria: * Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis. * LMS: * Any grade LMS can be included * Minimum size of LMS tumor should be 5 cm * LPS: * Diagnosis should be confirmed based on MDM2 (Mouse double minute 2 homolog) and CDK4 (Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while proof of MDM2 amplification is highly recommended. * All grade 3 DDLPS can be included. * DDLPS with confirmed grade 2 on biopsy can be included when: * The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy). * The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high) * Unifocal tumour * Resectable tumour: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcoma team. A patient is not considered resectable when the expectation is that only an R2 resection is feasible. * Criteria for non-resectability are: * Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein * Involvement of bone * Growth into the spinal canal * Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium * Infiltration of multiple major organs like liver, pancreas and or major vessels * Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. CT thorax abdomen pelvis with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen \& pelvis * Collection of tumour tissue for central pathology review is mandatory. * For patients with LMS: if there is not enough tissue for assessing the grading, this is acceptable. * If tumour tissue is not available for the central pathology review, patient will not be eligible. * If the biopsy was not done or the FFPE of the biopsy not available but at least 10 unstained slides or one pathological block are available for the central review, that will be considered as acceptable. * For the biopsy if fine needle aspiration (FNA) is performed instead of core needle biopsy (CNB) recommended by the standard guidelines, please contact the EORTC medical monitors for further evaluation. * Collection of tumour tissue and blood samples for translational research is mandatory. * In case there is not enough tissue for TR, a new biopsy is not required and if the patient fulfils all other eligibility criteria, he/she will be eligible. * If the blood samples are not collected, patient will not be eligible. * If the patient refuses the collection of biomaterial for TR, patient will not be eligible even if he/she fulfils all other eligibility criteria * ≥ 18 years old (no upper age limit) * WHO performance status ≤ 2 * Adequate haematological and organ function * American Society of Anaesthesiologist (ASA) score \< 3 * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization. Note: a woman is considered of childbearing potential, i.e., fertile, if she is following menarche. She remains of childbearing potential until she becomes post-menopausal or permanently sterile.Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 consecutive months without menses, a single FSH measurement is insufficient. * WOCBP in both arms should use highly effective birth control measures, during the study treatment period and for at least 6 months after the last dose of chemotherapy or date of surgery (except for women receiving chemotherapy with ifosfamide who should continue contraception until 1 year after last day of treatment). A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. * For men in the experimental arm: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm. * Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6months after the last study treatment. * Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion criteria: * Sarcoma originating from bone structure, abdominal or gynecological viscera * Extension through the sciatic notch or across the diaphragm * Metastatic disease * Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour * Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients * Congestive heart failure * Angina pectoris * Myocardial infarction within 1 year before randomization * Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy. Note: in case of high blood pressure: 1) initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 2) blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 150/90mmHg in order for a patient to be eligible for the study. * Uncontrolled cardiac arrhythmia * Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones * Active and uncontrolled infections * Vaccination with live vaccines within 30 days prior to study entry * Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow. * Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer. * Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum. * Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method. * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial * Known contraindication to imaging tracer and to MRI 2. Selection criteria for STREXIT 2 * Patients with histologically proven primary resectable localized high-risk DDLPS or LMS of retroperitoneal space or infra-peritoneal spaces of pelvis (as described in the inclusion criteria of STRASS 2) and amenable to receive chemotherapy but for whom the list of eligibility criteria for the study is too restrictive (tumour grading not available, inadequate organ function, concomitant diseases) * Patients who meet all eligibility criteria of STRASS 2 but do not consent to randomization or are not enrolled for any other reason. * Patients enrolled in a Registry collecting data on primary RPS patients in the centres participating in STRASS 2 (e.g., RESAR) and who satisfy the above criteria. 3. Selection criteria for preferences for neoadjuvant chemotherapy in STRASS 2 substudy All patients recruited to STRASS 2 in participating centres (Australia +/- international sites) that are able to read, comprehend and write in English at a sufficient level to complete study materials.

Interventions

PROCEDURE

Surgery

DRUG

Preoperative chemotherapy

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Conditions

Retroperitoneal SarcomaLiposarcomaLeiomyosarcoma

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

UCI Health-Chao Family Comp CC and Ambulatory Care

Irvine, California 92612

United States

UC San Diego Moores Cancer Center

La Jolla, California 92093

United States

UC Irvine Health/Chao Family Comprehensive Ca Ctr

Orange, California 92668

United States

UCHealth University of Colorado Hospital

Aurora, Colorado 80045

United States

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut 06418

United States

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut 06824

United States

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut 06033

United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut 06830

United States

Smilow Cancer Hospital Care Center - Guiford

Guilford, Connecticut 06437

United States

Smilow Cancer Hospital Care Ctr at Saint Francis

Hartford, Connecticut 06105

United States

Yale University

New Haven, Connecticut 06520

United States

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut 06385

United States

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut 06902

United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut 06611

United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut 06708

United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut 06385

United States

Univ of Florida Health Science Ctr - Gainesville

Gainesville, Florida 32610

United States

Mayo Clinic in Florida

Jacksonville, Florida 32224

United States

Moffitt Cancer Center-International Plaza

Tampa, Florida 33607

United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida 33612

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Northwestern University

Chicago, Illinois 60611

United States

Rush University Medical Center

Chicago, Illinois 60612

United States

University of Illinois at Chicago MBCCOP

Chicago, Illinois 60612

United States

Indiana Univ/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana 46202

United States

University of Kansas Cancer Center

Kansas City, Kansas 66160

United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas 66210

United States

University of Kansas Hospital-Westwood Cancer Ctr

Westwood, Kansas 66205

United States

James Graham Brown Ca Ctr at Univ of Louisville

Louisville, Kentucky 40202

United States

UofL Health Medical Center Northeast

Louisville, Kentucky 40245

United States

LSU Health Baton Rouge-North Clinic

Baton Rouge, Louisiana 70805

United States

Our Lady of The Lake Hospital

Baton Rouge, Louisiana 70808

United States

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana 70808

United States

Johns Hopkins Univ/Sidney Kimmel Cancer Center

Baltimore, Maryland 21205

United States

Dana-Farber/Harvard Cancer Center

Boston, Massachusetts 02215

United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan 48109

United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota 56601

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Siteman Cancer Center-West County

Creve Coeur, Missouri 63141

United States

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri 63110

United States

Siteman Cancer Center-South Country

St Louis, Missouri 63129

United States

Nebraska Medicine-Bellevue

Bellevue, Nebraska 68123

United States

Nebraska Medicine-Bellevue

Omaha, Nebraska 68118

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Dartmouth Hitchcock Med Ctr/Dartmouth Cancer Ctr

Lebanon, New Hampshire 03756

United States

Cooper Hospital University Medical Center

Camden, New Jersey 08103

United States

HMH-Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Jersey Shore University Medical Center

Neptune City, New Jersey 07753

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08903

United States

John Theurer Cancer Center at From Road

Paramus, New Jersey 07652

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York 11042

United States

North Shore University Hospital

Manhasset, New York 11030

United States

NYU Langone Hospital - Long Island

Mineola, New York 11501

United States

Long Island Jewish Medical Center

New Hyde Park, New York 11040

United States

Laura and Issac Perlmutter Ca Ctr at NYU Langone

New York, New York 10016

United States

University of Rochester

Rochester, New York 14642

United States

Stony Brook University Medical Center

Stony Brook, New York 11794

United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina 28203

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Sanford Bismarck Medical Center

Bismarck, North Dakota 58501

United States

Sanford Broadway Medical Center

Fargo, North Dakota 58122

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota 58122

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Saint Vincent Hospital

Erie, Pennsylvania 16544

United States

Jefferson Hospital

Jefferson Hills, Pennsylvania 15025

United States

Forbes Hospital

Monroeville, Pennsylvania 15146

United States

Allegheny Valley Hospital

Natrona Heights, Pennsylvania 15065

United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

Pennsylvania Hospital

Philadelphia, Pennsylvania 19107

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania 19111

United States

Allegheny General Hospital

Pittsburgh, Pennsylvania 15212

United States

West Penn Hospital

Pittsburgh, Pennsylvania 15224

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Wexford Health and Wellness Pavilion

Wexford, Pennsylvania 15090

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island 02891

United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota 57104

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota 57117

United States

University of Tennessee - Knoxville

Knoxville, Tennessee 37920

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas 75390

United States

M D Anderson Cancer Center

Houston, Texas 77030

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah 84132

United States

University of Vermont Medical Center

Burlington, Vermont 05401

United States

Vermont Regional Cancer Center

Burlington, Vermont 05405

United States

VCU Massey Cancer Center at Hanover Medical Park

Mechanicsville, Virginia 23116

United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia 23235

United States

Virginia Commonwealth Univ/Massey Cancer Center

Richmond, Virginia 23298

United States

Carilion Roanoke Memorial Hospital

Roanoke, Virginia 24014

United States

VCU Community Memorial Health Center

South Hill, Virginia 23970

United States

FHCC South Lake Union

Seattle, Washington 98109

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

University of Washington Medical Center - Montlake

Seattle, Washington 98195

United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin 54701

United States

Marshfield Medical Center

Marshfield, Wisconsin 54449

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Marshfield Medical Center

Minocqua, Wisconsin 54548

United States

Marshfield Medical Center

Rice Lake, Wisconsin 54868

United States

Marshfield Med Ctr-River Region at Stevens Point

Stevens Point, Wisconsin 54482

United States

Marshfield Medical Center

Weston, Wisconsin 54476

United States

Princess Alexandra Hospital - University Of Queensland

Woolloongabba, Queensland QLD 4102

Australia

Peter Maccallum Cancer Institute

Melbourne, Victoria 3000

Australia

Chris O'Brian Life House - Chris O'Brien Lifehouse

Camperdown, 2050

Australia

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia V5Z 4E6

Canada

London Regional Cancer Center

London, Ontario N6A 4L6

Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario

Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec H1T 2M4

Canada

The Research Institute of the McGill University Health Centre

Montreal, Quebec H4A3J1

Canada

Mount Sinai Hospital

Toronto,

Canada

Bank Of Cyprus Oncology Centre

Stróvolos, 2006

Cyprus

Masaryk Memorial Cancer Institute

Brno, 656 53

Czechia

University Hospital Motol

Prague, 150 06

Czechia

Herlev Hospital - University Copenhagen

Herlev, Copenhagen 2730

Denmark

Aarhus University Hospitals - Aarhus University Hospital-Skejby

Aarhus, 8250

Denmark

Centre Leon Berard

Lyon, 69008

France

Institut du Cancer de Montpellier

Montpellier, 34298

France

Institut Curie- Hopital de Paris

Paris, 75248

France

Hopitaux Universitaires de Strasbourg - Hautepierre

Strasbourg, 67098

France

Institut Gustave Roussy

Villejuif, 94805

France

Universitaetsmedizin Goettingen - Georg-August Universitaet

Goettigen, Lower Saxony 37075

Germany

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307

Germany

UniversitaetsMedizin Mannheim

Mannheim, 68167

Germany

Centro Di Riferimento Oncologico

Aviano, 33081

Italy

IRCCS - Fondazione Piemonte Inst di Candiolo

Candiolo,

Italy

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola,

Italy

IRCCS - Istituto Nazionale dei Tumori

Milan, 20133

Italy

Istituto Clinico Humanitas

Milan,

Italy

Istituto Europeo di Oncologia

Milan,

Italy

IRCCS - Istituto Oncologico Veneto

Padova,

Italy

Policlinico Universitario Campus Bio-Medico- Oncology Center

Roma,

Italy

Kyushu University Hospital

Higashiku, Fukuoka 812-8582

Japan

Yokohama City University Hospital

Yokohama, Kanagawa 236-0004

Japan

Kanagawa Cancer Center

Yokohama, Kanagawa 241-8515

Japan

Tohoku University Hospital

Sendai, Miyagi 780-8574

Japan

Aichi Cancer Center

Chikusa-ku, Nagoya 464-8681

Japan

Nagoya University Hospital

Shōwaku, Nagoya 466-8550

Japan

Niigata University Medical and Dental Hospital

Niigata, Niigata 951-8520

Japan

Okayama University Hospital

Kita-ku, Okayama-ken 700-8558

Japan

Osaka International Cancer Institute

Chuo-ku, Osaka 541-8567

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo 135-8550

Japan

Saitama Medical Center, Jichi Medical University

Saitama, 330-8503

Japan

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, 1066

Netherlands

Leiden University Medical Centre

Leiden, 2300 RC

Netherlands

Radboudumc - Radboud University Medical Center Nijmegen

Nijmegen, 6525

Netherlands

Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw,

Poland

National Cancer Institute

Bratislava, SK 833 10

Slovakia

Hospital De La Santa Creu I Sant Pau

Barcelona, 08041

Spain

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol

Barcelona,

Spain

Hospital General Universitario Gregorio Maranon

Madrid, 28007

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario San Carlos

Madrid, 28040

Spain

University Hospitals Birmingham - Queen Elisabeth Medical Centre

Birmingham, B15 2TH

United Kingdom

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

Glasgow,

United Kingdom

Leeds Teaching Hospitals NHS Trust - St. James's University Hospital

Leeds, LS9 7TF

United Kingdom

the Royal Marsden Hospital

London,

United Kingdom

Clatterbridge cancer center

Metropolitan Borough of Wirral, CH63 4JY

United Kingdom

Newcastle Hospitals - Freeman Hospital, Northern Centre For Cancer Care

Newcastle, NE7 7DN

United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB

United Kingdom

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, OX3 7LE

United Kingdom