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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04031677
Other study ID # EORTC 1809-STBSG
Secondary ID EA7211SR.7ASSG45
Status Recruiting
Phase Phase 3
First received
Last updated
Start date January 20, 2021
Est. completion date April 21, 2028

Study information

Verified date April 2024
Source European Organisation for Research and Treatment of Cancer - EORTC
Contact EORTC HQ
Phone +3227741611
Email 1809@eortc.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 250
Est. completion date April 21, 2028
Est. primary completion date April 21, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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), has no necrosis on the biopsy but clear necrosis on imaging. - The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high) - Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides must be available at baseline for histological central review. - Unifocal tumor - Absence of extension through the sciatic notch or across the diaphragm - Resectable tumor: 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 patients 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 - Tumor not previously treated (no previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy) - Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging within the 28 days prior to randomization. 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. - = 18 years old (no upper age limit) - WHO (World Health Organization) performance status = 2 - Adequate haematological and organ function: - Haematological: haemoglobin > 9.0 g/dL or 5.6 mmol/L, absolute neutrophils > 1.5 x 109/L, platelets > 100 x 109/L Note: Platelet transfusions is allowed to achieve these baseline values - Renal: estimated glomerular filtration rate (eGFR) > 50 ml/min/m2; No proteinuria CTCAE = grade 2; - Hepatic: Bilirubin = 1.0 times upper limit of normal (1.0xULN) of institutional limits, ALT (alanine aminotransferase) and/or AST (aspartate transaminase) =1.5 x ULN. If isolated elevated bilirubin <2 x ULN and Gilberts syndrome suspected, suggest repeating bloods after food. If bilirubin improves to meet the criteria above this is acceptable. More severe persistent hepatic impairment of whatever cause would exclude the patient from treatment till resolved. - Heart: Clinically normal cardiac function based on left ventricular ejection fraction (LVEF = 50%) as assessed either by multi-gated acquisition scan (MUGA) or cardiac ultrasound and 12 lead ECG without clinically relevant abnormalities. - American Society of Anesthesiologist (ASA) score < 3 - Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment or surgery. Note: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post menopausal unless 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 months of amenorrhea, a single FSH measurement is insufficient.. - Patients of childbearing / reproductive potential should use highly effective birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment or date of surgery. 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. Such methods include: - Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - Intrauterine device (IUD) - Intrauterine hormone-releasing system (IUS) - Bilateral tubal occlusion - Vasectomized partner - Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient) - Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6 months after the last study treatment. - Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria: - Sarcoma originated from bone structure, abdominal or gynecological viscera - Metastatic disease - Tumors with extension through the sciatic notch or across the diaphragm - Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients - Persistent myelosuppression - Myocardial infarction within the last 6 months - Uncontrolled cardiac arrhythmia - Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² EpiADM) 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 presumably cured prostate cancer. - Uncontrolled severe illness, infection,medical condition (including, uncontrolled diabetes or hypertension), 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

Study Design


Related Conditions & MeSH terms


Intervention

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 Note: the recommended dose of Ifosfamide can be modified according to national/institutional guidelines, given that the minimum threshold must be 7.5 g/m2 per cycle. - LMS: ADM 75 mg/m2 + DTIC 1g/m2 Q3 weeks

Locations

Country Name City State
Australia Chris O'Brian Life House - Chris O'Brien Lifehouse Camperdown
Australia Peter Maccallum Cancer Institute Melbourne Victoria
Australia Princess Alexandra Hospital - University Of Queensland Woolloongabba Queensland
Canada London Regional Cancer Center London Ontario
Canada Hopital Maisonneuve Rosemont Montréal Quebec
Canada The Research Institute of the McGill University Health Centre Montréal Quebec
Canada The Ottawa Hospital - General Campus Ottawa Ontario
Canada Mount Sinai Hospital Toronto
Canada BCCA - Vancouver Cancer Centre Vancouver British Columbia
Cyprus Bank Of Cyprus Oncology Centre Stróvolos
Czechia Masaryk Memorial Cancer Institute Brno
Denmark Aarhus University Hospitals - Aarhus University Hospital-Skejby Aarhus
Denmark Herlev Hospital - University Copenhagen Herlev Copenhagen
France 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
Germany Universitaetsklinikum Carl Gustav Carus Dresden
Germany Universitaetsmedizin Goettingen - Georg-August Universitaet Goettigen Lower Saxony
Germany UniversitaetsMedizin Mannheim Mannheim
Italy 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 Milano
Italy Istituto Europeo di Oncologia Milano
Italy IRCCS - Istituto Oncologico Veneto Padova
Italy Policlinico Universitario Campus Bio-Medico- Oncology Center Roma
Japan Aichi Cancer Center Chikusa-ku Nagoya
Japan National Cancer Center Hospital Chuo-ku Tokyo
Japan Osaka International Cancer Institute Chuo-ku Osaka
Japan Kyushu University Hospital Higashi-ku Fukuoka
Japan Okayama University Hospital Kita-ku Okayama
Japan Cancer Institute Hospital of JFCR Koto-ku Tokyo
Japan Niigata University Medical and Dental Hospital Niigata City Niigata
Japan Saitama Medical Center, Jichi Medical University Saitama
Japan Tohoku University Hospital Sendai Miyagi
Japan Nagoya University Hospital Showa-ku Nagoya
Japan Kanagawa Cancer Center Yokohama Kanagawa
Japan Yokohama City University Hospital Yokohama Kanagawa
Netherlands The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis Amsterdam
Netherlands Leiden University Medical Centre Leiden
Netherlands Radboudumc - Radboud University Medical Center Nijmegen Nijmegen
Poland Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska-Curie National Research Institute of Oncology Warsaw
Slovakia National Cancer Institute Bratislava
Spain 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
United Kingdom 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 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 Clatterbridge cancer center Wirral
United States University of Michigan Comprehensive Cancer Center Ann Arbor Michigan
United States Emory University Hospital Midtown Atlanta Georgia
United States UCHealth University of Colorado Hospital Aurora Colorado
United States Johns Hopkins Univ/Sidney Kimmel Cancer Center Baltimore Maryland
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 Nebraska Medicine-Bellevue Bellevue Nebraska
United States Sanford Joe Lueken Cancer Center Bemidji Minnesota
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States Dana-Farber/Harvard Cancer Center Boston Massachusetts
United States Roswell Park Cancer Institute Buffalo New York
United States Northwestern University Chicago Illinois
United States University of Illinois at Chicago MBCCOP Chicago Illinois
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Siteman Cancer Center-West County Creve Coeur Missouri
United States Smilow Cancer Hospital-Derby Care Center Derby Connecticut
United States City of Hope Comprehensive Cancer Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States Smilow Cancer Hospital Care Center-Fairfield Fairfield Connecticut
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Roger Maris Cancer Center Fargo North Dakota
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 M D Anderson Cancer Center Houston Texas
United States Mayo Clinic in Florida Jacksonville Florida
United States University of Kansas Cancer Center Kansas City Kansas
United States Dartmouth Hitchcock Med Ctr/Dartmouth Cancer Ctr Lebanon New Hampshire
United States Marshfield Medical Center Marshfield Wisconsin
United States VCU Massey Cancer Center at Hanover Medical Park Mechanicsville Virginia
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Marshfield Medical Center Minocqua Wisconsin
United States Yale University New Haven Connecticut
United States Yale-New Haven Hospital North Haven Medical Center North Haven Connecticut
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Nebraska Medicine-Bellevue Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States UC Irvine Health/Chao Family Comprehensive Ca Ctr Orange California
United States University of Kansas Cancer Center-Overland Park Overland Park Kansas
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Pennsylvania Hospital Philadelphia Pennsylvania
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States Mayo Clinic Hospital in Arizona Phoenix Arizona
United States UPMC Hillman Cancer Center Pittsburgh Pennsylvania
United States Oregon Health and Science University Portland Oregon
United States Marshfield Medical Center Rice Lake Wisconsin
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 Mayo Clinic Rochester Minnesota
United States University of Rochester Rochester New York
United States Siteman Cancer Center-South Country Saint Louis Missouri
United States Washington University School of Medicine - Siteman Cancer Center Saint Louis Missouri
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
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 Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States VCU Community Memorial Health Center South Hill Virginia
United States Smilow Cancer Hospital Care Center at Long Ridge Stamford Connecticut
United States Marshfield Med Ctr-River Region at Stevens Point Stevens Point Wisconsin
United States Moffitt Cancer Center Tampa Florida
United States Moffitt Cancer Center - McKinley Campus Tampa Florida
United States Moffitt Cancer Center-International Plaza Tampa Florida
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 Smilow Cancer Hospital Care Center - Westerly Westerly Rhode Island
United States Marshfield Medical Center Weston Wisconsin
United States University of Kansas Hospital-Westwood Cancer Ctr Westwood Kansas

Sponsors (6)

Lead Sponsor Collaborator
European Organisation for Research and Treatment of Cancer - EORTC Anticancer Fund, Belgium, Australia and New Zealand Sarcoma Association, Canadian Cancer Trials Group, ECOG-ACRIN Cancer Research Group, Japan Clinical Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Cyprus,  Czechia,  Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Disease free survival Disease free survival will be measured from the data of randomization (as reference) to the date of recurrence or death, whichever occurs first. 7 years from first patient in
Secondary Overall survival (OS) OS will be measured from the date of randomization to the date of death, whatever the cause. 8 years from first patient in
Secondary Local recurrence free survival Local recurrence free survival will be measured from the date of randomization to the date of recurrence (local) or death, whichever occurs first. 8 years from first patient in
Secondary Recurrence free survival Recurrence free survival will be measured from the date of randomization to the date of recurrence (local or distant) or death, whichever occurs first. 8 years from first patient in
Secondary Distant metastases free survival Distant metastases free survival will be measured from the date of randomization to the date of distant metastases or death, whichever occurs first. 8 years from first patient in
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