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RECRUITING

NCT04031677

PHASE3

Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma

Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

View on ClinicalTrials.gov

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.

Official title: A Randomized Phase III Study of Neoadjuvant Chemotherapy Followed by Surgery Versus Surgery Alone for Patients With High Risk RetroPeritoneal Sarcoma (RPS)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

250

Start Date

2021-01-20

Completion Date

2028-04-21

Last Updated

2026-03-31

Healthy Volunteers

Conditions

Retroperitoneal Sarcoma Liposarcoma Leiomyosarcoma

Interventions

PROCEDURE

Surgery

Large en-bloc curative-intent surgery

DRUG

Preoperative chemotherapy

* High grade LPS: ADM 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m2 Q3 weeks * LMS: ADM 75 mg/m2 + DTIC 1g/m2 Q3 weeks Note: the recommended dose of Doxorubicin (or Epirubicin) can be modified according to national/institutional guidelines, given that the minimal threshold must be Doxorubicin 60 mg/m2 per cycle (or the equivalent Epirubicin 95 mg/m2 per cycle); the recommended dose of Ifosfamide can be modified according to national/institutional guidelines, given that the minimal threshold must be 7.5 g/m2 per cycle; the recommended dose of Dacarbazine can be modified according to national/institutional guidelines, given that the minimal threshold must be 900 mg/m2 per cycle. The schedule of administration of above chemotherapies can be modified according to national/institutional guidelines provided that the minimal threshold of doses, and the treatment periods with chemotherapies remain the same.

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.

Locations (164)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

UCI Health-Chao Family Comp CC and Ambulatory Care

Irvine, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

UC Irvine Health/Chao Family Comprehensive Ca Ctr

Orange, California, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guiford

Guilford, Connecticut, United States

Smilow Cancer Hospital Care Ctr at Saint Francis

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Univ of Florida Health Science Ctr - Gainesville

Gainesville, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Illinois at Chicago MBCCOP

Chicago, Illinois, United States

Indiana Univ/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

University of Kansas Hospital-Westwood Cancer Ctr

Westwood, Kansas, United States

James Graham Brown Ca Ctr at Univ of Louisville

Louisville, Kentucky, United States

UofL Health Medical Center Northeast

Louisville, Kentucky, United States

LSU Health Baton Rouge-North Clinic

Baton Rouge, Louisiana, United States

Our Lady of The Lake Hospital

Baton Rouge, Louisiana, United States

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana, United States

Johns Hopkins Univ/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Dana-Farber/Harvard Cancer Center

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Siteman Cancer Center-West County

Creve Coeur, Missouri, United States

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

Siteman Cancer Center-South Country

St Louis, Missouri, United States

Nebraska Medicine-Bellevue

Bellevue, Nebraska, United States

Nebraska Medicine-Bellevue

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Renown Regional Medical Center

Reno, Nevada, United States

Dartmouth Hitchcock Med Ctr/Dartmouth Cancer Ctr

Lebanon, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

HMH-Hackensack University Medical Center

Hackensack, New Jersey, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

John Theurer Cancer Center at From Road

Paramus, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

NYU Langone Hospital - Long Island

Mineola, New York, United States

Laura and Issac Perlmutter Ca Ctr at NYU Langone

New York, New York, United States

University of Rochester

Rochester, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

Saint Vincent Hospital

Erie, Pennsylvania, United States

Jefferson Hospital

Jefferson Hills, Pennsylvania, United States

Forbes Hospital

Monroeville, Pennsylvania, United States

Allegheny Valley Hospital

Natrona Heights, Pennsylvania, United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

West Penn Hospital

Pittsburgh, Pennsylvania, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Wexford Health and Wellness Pavilion

Wexford, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

University of Tennessee - Knoxville

Knoxville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Vermont Regional Cancer Center

Burlington, Vermont, United States

VCU Massey Cancer Center at Hanover Medical Park

Mechanicsville, Virginia, United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, United States

Virginia Commonwealth Univ/Massey Cancer Center

Richmond, Virginia, United States

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, United States

VCU Community Memorial Health Center

South Hill, Virginia, United States

FHCC South Lake Union

Seattle, Washington, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, United States

Marshfield Medical Center

Marshfield, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Marshfield Medical Center

Minocqua, Wisconsin, United States

Marshfield Medical Center

Rice Lake, Wisconsin, United States

Marshfield Med Ctr-River Region at Stevens Point

Stevens Point, Wisconsin, United States

Marshfield Medical Center

Weston, Wisconsin, United States

Princess Alexandra Hospital - University Of Queensland

Woolloongabba, Queensland, Australia

Peter Maccallum Cancer Institute

Melbourne, Victoria, Australia

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

Camperdown, Australia

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

London Regional Cancer Center

London, Ontario, Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec, Canada

The Research Institute of the McGill University Health Centre

Montreal, Quebec, Canada

Mount Sinai Hospital

Toronto, Canada

Bank Of Cyprus Oncology Centre

Stróvolos, Cyprus

Masaryk Memorial Cancer Institute

Brno, Czechia

Herlev Hospital - University Copenhagen

Herlev, Copenhagen, Denmark

Aarhus University Hospitals - Aarhus University Hospital-Skejby

Aarhus, Denmark

Centre Leon Berard

Lyon, France

Institut du Cancer de Montpellier

Montpellier, France

Institut Curie- Hopital de Paris

Paris, France

Hopitaux Universitaires de Strasbourg - Hautepierre

Strasbourg, France

Institut Gustave Roussy

Villejuif, France

Universitaetsmedizin Goettingen - Georg-August Universitaet

Goettigen, Lower Saxony, Germany

Universitaetsklinikum Carl Gustav Carus

Dresden, Germany

UniversitaetsMedizin Mannheim

Mannheim, Germany

Centro Di Riferimento Oncologico

Aviano, 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, 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, Japan

Yokohama City University Hospital

Yokohama, Kanagawa, Japan

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Aichi Cancer Center

Chikusa-ku, Nagoya, Japan

Nagoya University Hospital

Shōwaku, Nagoya, Japan

Niigata University Medical and Dental Hospital

Niigata, Niigata, Japan

Okayama University Hospital

Kita-ku, Okayama-ken, Japan

Osaka International Cancer Institute

Chuo-ku, Osaka, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Saitama Medical Center, Jichi Medical University

Saitama, Japan

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

Amsterdam, Netherlands

Leiden University Medical Centre

Leiden, Netherlands

Radboudumc - Radboud University Medical Center Nijmegen

Nijmegen, Netherlands

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

Warsaw, Poland

National Cancer Institute

Bratislava, Slovakia

Hospital De La Santa Creu I Sant Pau

Barcelona, Spain

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

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Hospital Universitario San Carlos

Madrid, Spain

University Hospitals Birmingham - Queen Elisabeth Medical Centre

Birmingham, 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, United Kingdom

the Royal Marsden Hospital

London, United Kingdom

Clatterbridge cancer center

Metropolitan Borough of Wirral, United Kingdom

Newcastle Hospitals - Freeman Hospital, Northern Centre For Cancer Care

Newcastle, United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, United Kingdom

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, United Kingdom

Clinical Research Directory

Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (164)