Recruiting
Phase 3

Surgery with Chemotherapy

Sponsor:

European Organisation for Research and Treatment of Cancer - EORTC

Code:

NCT04031677

Conditions

Retroperitoneal Sarcoma

Liposarcoma

Leiomyosarcoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Surgery

Preoperative chemotherapy

Study Details

Brief 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.

Conditions

Retroperitoneal Sarcoma

Liposarcoma

Leiomyosarcoma

Study ID

NCT04031677

Start date

Jan 20, 2021

Status verified date

May, 2026

Completion date

Apr 21, 2028

Anticipated

Primary completion date

Apr 21, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

250 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Standard arm

Surgery alone

experimental: Experimental arm

Preoperative chemotherapy and surgery

Interventions

Surgery

Large en-bloc curative-intent surgery

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.

Primary outcome measure

  • Disease free survival [ Time Frame: 7 years from first patient in ]

Central Contacts and Locations

Central contacts

EORTC HQ

+32277416111809@eortc.org

Locations

Mayo Clinic Hospital in Arizona

Recruiting

Phoenix, Arizona, United States, 85054

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

UCI Health-Chao Family Comp CC and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

UC Irvine Health/Chao Family Comprehensive Ca Ctr

Recruiting

Orange, California, United States, 92668

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Smilow Cancer Hospital-Derby Care Center

Recruiting

Derby, Connecticut, United States, 06418

Smilow Cancer Hospital Care Center-Fairfield

Recruiting

Fairfield, Connecticut, United States, 06824

Smilow Cancer Hospital Care Center at Glastonbury

Recruiting

Glastonbury, Connecticut, United States, 06033

Smilow Cancer Hospital Care Center at Greenwich

Recruiting

Greenwich, Connecticut, United States, 06830

Smilow Cancer Hospital Care Center - Guiford

Recruiting

Guilford, Connecticut, United States, 06437

Smilow Cancer Hospital Care Ctr at Saint Francis

Recruiting

Hartford, Connecticut, United States, 06105

Yale University

Recruiting

New Haven, Connecticut, United States, 06520

Yale-New Haven Hospital North Haven Medical Center

Recruiting

North Haven, Connecticut, United States, 06385

Smilow Cancer Hospital Care Center at Long Ridge

Recruiting

Stamford, Connecticut, United States, 06902

Smilow Cancer Hospital Care Center-Trumbull

Recruiting

Trumbull, Connecticut, United States, 06611

Smilow Cancer Hospital-Waterbury Care Center

Recruiting

Waterbury, Connecticut, United States, 06708

Smilow Cancer Hospital Care Center - Waterford

Recruiting

Waterford, Connecticut, United States, 06385

Univ of Florida Health Science Ctr - Gainesville

Recruiting

Gainesville, Florida, United States, 32610

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224

Moffitt Cancer Center-International Plaza

Recruiting

Tampa, Florida, United States, 33607

Moffitt Cancer Center - McKinley Campus

Recruiting

Tampa, Florida, United States, 33612

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Rush University Medical Center

Recruiting

Chicago, Illinois, United States, 60612

University of Illinois at Chicago MBCCOP

Recruiting

Chicago, Illinois, United States, 60612

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

University of Kansas Hospital-Westwood Cancer Ctr

Recruiting

Westwood, Kansas, United States, 66205

James Graham Brown Ca Ctr at Univ of Louisville

Recruiting

Louisville, Kentucky, United States, 40202

UofL Health Medical Center Northeast

Recruiting

Louisville, Kentucky, United States, 40245

LSU Health Baton Rouge-North Clinic

Recruiting

Baton Rouge, Louisiana, United States, 70805

Our Lady of The Lake Hospital

Recruiting

Baton Rouge, Louisiana, United States, 70808

Our Lady of the Lake Physician Group

Recruiting

Baton Rouge, Louisiana, United States, 70808

Dana-Farber/Harvard Cancer Center

Recruiting

Boston, Massachusetts, United States, 02215

University of Michigan Comprehensive Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Sanford Joe Lueken Cancer Center

Recruiting

Bemidji, Minnesota, United States, 56601

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Siteman Cancer Center-West County

Recruiting

Creve Coeur, Missouri, United States, 63141

Washington University School of Medicine - Siteman Cancer Center

Recruiting

St Louis, Missouri, United States, 63110

Siteman Cancer Center-South Country

Recruiting

St Louis, Missouri, United States, 63129

Nebraska Medicine-Bellevue

Recruiting

Bellevue, Nebraska, United States, 68123

Nebraska Medicine-Bellevue

Recruiting

Omaha, Nebraska, United States, 68118

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Renown Regional Medical Center

Recruiting

Reno, Nevada, United States, 89502

Cooper Hospital University Medical Center

Recruiting

Camden, New Jersey, United States, 08103

HMH-Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Jersey Shore University Medical Center

Recruiting

Neptune City, New Jersey, United States, 07753

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08903

John Theurer Cancer Center at From Road

Recruiting

Paramus, New Jersey, United States, 07652

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Northwell Health/Center for Advanced Medicine

Recruiting

Lake Success, New York, United States, 11042

North Shore University Hospital

Recruiting

Manhasset, New York, United States, 11030

NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Long Island Jewish Medical Center

Recruiting

New Hyde Park, New York, United States, 11040

Laura and Issac Perlmutter Ca Ctr at NYU Langone

Recruiting

New York, New York, United States, 10016

University of Rochester

Recruiting

Rochester, New York, United States, 14642

Stony Brook University Medical Center

Recruiting

Stony Brook, New York, United States, 11794

Carolinas Medical Center/Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28203

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

Saint Vincent Hospital

Recruiting

Erie, Pennsylvania, United States, 16544

Jefferson Hospital

Recruiting

Jefferson Hills, Pennsylvania, United States, 15025

Forbes Hospital

Recruiting

Monroeville, Pennsylvania, United States, 15146

Allegheny Valley Hospital

Recruiting

Natrona Heights, Pennsylvania, United States, 15065

University of Pennsylvania/Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Pennsylvania Hospital

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Thomas Jefferson University Hospital

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Fox Chase Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Allegheny General Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

West Penn Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15224

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Wexford Health and Wellness Pavilion

Recruiting

Wexford, Pennsylvania, United States, 15090

Rhode Island Hospital

Recruiting

Providence, Rhode Island, United States, 02903

Smilow Cancer Hospital Care Center - Westerly

Recruiting

Westerly, Rhode Island, United States, 02891

University of Tennessee - Knoxville

Recruiting

Knoxville, Tennessee, United States, 37920

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

UT Southwestern/Simmons Cancer Center-Dallas

Recruiting

Dallas, Texas, United States, 75390

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84132

University of Vermont Medical Center

Recruiting

Burlington, Vermont, United States, 05401

Vermont Regional Cancer Center

Recruiting

Burlington, Vermont, United States, 05405

VCU Massey Cancer Center at Hanover Medical Park

Recruiting

Mechanicsville, Virginia, United States, 23116

VCU Massey Cancer Center at Stony Point

Recruiting

Richmond, Virginia, United States, 23235

Virginia Commonwealth Univ/Massey Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Carilion Roanoke Memorial Hospital

Recruiting

Roanoke, Virginia, United States, 24014

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

University of Washington Medical Center - Montlake

Recruiting

Seattle, Washington, United States, 98195

Marshfield Medical Center-EC Cancer Center

Recruiting

Eau Claire, Wisconsin, United States, 54701

Marshfield Medical Center

Recruiting

Marshfield, Wisconsin, United States, 54449

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Marshfield Medical Center

Recruiting

Minocqua, Wisconsin, United States, 54548

Marshfield Medical Center

Recruiting

Rice Lake, Wisconsin, United States, 54868

Marshfield Med Ctr-River Region at Stevens Point

Recruiting

Stevens Point, Wisconsin, United States, 54482

Marshfield Medical Center

Recruiting

Weston, Wisconsin, United States, 54476

BCCA - Vancouver Cancer Centre

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

London Regional Cancer Center

Recruiting

London, Ontario, Canada, N6A 4L6

The Ottawa Hospital - General Campus

Recruiting

Ottawa, Ontario, Canada

Hopital Maisonneuve Rosemont

Recruiting

Montreal, Quebec, Canada, H1T 2M4

The Research Institute of the McGill University Health Centre

Recruiting

Montreal, Quebec, Canada, H4A3J1

Mount Sinai Hospital

Recruiting

Toronto, Canada

More Information

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Last update posted

May 22, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by European Organisation for Research and Treatment of Cancer - EORTC on 2026-05-22.