Sarcoma (Soft Tissue Cancer)

EA7211 /STRASS 2



A Randomized Study Investigating Preoperative Chemotherapy Followed by Surgery versus Surgery Alone in Patients with High Risk Retroperitoneal Sarcoma, STRASS2 Trial

STATUS: Active


This phase III trial compares the effect of adding chemotherapy (doxorubicin or epirubicin hydrochloride [epirubicin] with ifosfamide or dacarbazine) before standard surgery versus surgery alone in improving long-term survival in patients with retroperitoneal sarcomas that are able to be removed by surgery (resectable). Chemotherapy drugs, such as doxorubicin, epirubicin, ifosfamide, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller and easier to remove and may increase patient survival, compared to surgery alone.
  • Histologically proven primary high risk leiomyosarcoma (LMS) or liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis * LMS: ** Grades 2 and 3 LMS of minimum size 5 cm * LPS (diagnosis based on MDM2 and CDK4 expression on immunohistochemistry [IHC]; additional proof of MDM2 amplification is highly recommended but not mandatory): ** Grade 3 DDLPS OR ** Confirmed grade 2 DDLPS on biopsy only if: *** Federation Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) score = 5 AND clear necrosis on imaging (whether or not present on the biopsy) OR *** High risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)

  • Unifocal tumor

  • Resectable tumor: resectability is based on pre-operative imaging performed within 28 days before randomization (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 leimyosarcoma towards the right atrium ** Infiltration of multiple major organs like liver, pancreas and or major vessels

  • Patient must have radiologically measurable disease (Response Evaluation Criteria in Solid Tumors [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

  • Collection of tumor tissue and blood samples for central pathology review and translational research are mandatory. If tumor tissue is not available and/or patient does not consent, patient will not be eligible for this trial

  • >= 18 years old (no upper age limit)

  • World Health Organization (WHO) performance status =< 2

  • Hemoglobin > 9.0 g/dL or 5.6 mmol/L (within 21 days prior to randomization) * Note: Platelet transfusions is allowed to achieve these baseline values; red blood cell transfusion is not allowed

  • Absolute neutrophils > 1.5 x 10^9/L (within 21 days prior to randomization) * Note: Platelet transfusions is allowed to achieve these baseline values; red blood cell transfusion is not allowed

  • Platelets > 100 x 10^9/L (within 21 days prior to randomization) * Note: Platelet transfusions is allowed to achieve these baseline values; red blood cell transfusion is not allowed

  • Partial thromboplastin time =< 1.0 times upper limit of normal (1.0 x ULN) of institutional limits and prothrombin time =< 1.0 x upper limit of normal (ULN) of institutional limits (within 21 days prior to randomization) * Note: for patient under anticoagulant treatment international normalized ratio (INR) must be controlled and in the therapeutic target range according to local guidelines

  • Estimated glomerular filtration rate (eGFR) > 50 ml/min/m^2 (modification of diet in renal disease [MDRD] formula) (within 21 days prior to randomization)

  • No proteinuria >= grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) (within 21 days prior to randomization)

  • Bilirubin =< 1.0 x ULN of institutional limits (within 21 days prior to randomization). 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

  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 1.5 x ULN (within 21 days prior to randomization)

  • 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 electrocardiogram (ECG) without clinically relevant abnormalities (within 21 days prior to randomization)

  • American Society of Anaesthesiologist (ASA) score < 3

  • Women of child bearing 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 sterilization 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 6 months after the last study treatment

  • Before patient randomization, written informed consent must be given according to International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP), and national/local regulations

  • Sarcoma originating from bone structure, abdominal or gynecological viscera

  • Extension through the sciatic notch or across the diaphragm

  • Tumor grading not assessable from biopsy

  • Metastatic disease

  • Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumor

  • Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients

  • Congestive heart failure

  • Angina pectoris

  • Acute inflammatory heart disease

  • Myocardial infarction within 1 year before randomization

  • Uncontrolled arterial hypertension defined as blood pressure >= 150/100 mm Hg despite optimal medical therapy

  • Uncontrolled cardiac arrhythmia

  • Previous treatment with maximum cumulative doses (450 mg/m^2 doxorubicin or equivalent 900 mg/m^2 epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones

  • Active and uncontrolled infections, in particular urinary tract 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 =< 6 prostate cancer

  • Uncontrolled severe illness, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum

  • 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

United States
AZ
Phoenix
Mayo Clinic Hospital in Arizona
Contact: Site Public Contact

CA
Duarte
City of Hope Comprehensive Cancer Center
Contact: Site Public Contact
Email: becomingapatient@coh.org

Orange
UC Irvine Health/Chao Family Comprehensive Cancer Center
Contact: Site Public Contact
Email: ucstudy@uci.edu

CO
Aurora
UCHealth University of Colorado Hospital
Contact: Site Public Contact

CT
Derby
Smilow Cancer Hospital-Derby Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Fairfield
Smilow Cancer Hospital Care Center-Fairfield
Contact: Site Public Contact
Email: canceranswers@yale.edu

Glastonbury
Smilow Cancer Hospital Care Center at Glastonbury
Contact: Site Public Contact
Email: canceranswers@yale.edu

Greenwich
Smilow Cancer Hospital Care Center at Greenwich
Contact: Site Public Contact
Email: canceranswers@yale.edu

Guilford
Smilow Cancer Hospital Care Center - Guilford
Contact: Site Public Contact
Email: canceranswers@yale.edu

Hartford
Smilow Cancer Hospital Care Center at Saint Francis
Contact: Site Public Contact
Email: canceranswers@yale.edu

New Haven
Yale University
Contact: Site Public Contact
Email: canceranswers@yale.edu

North Haven
Yale-New Haven Hospital North Haven Medical Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Stamford
Smilow Cancer Hospital Care Center at Long Ridge
Contact: Site Public Contact
Email: canceranswers@yale.edu

Torrington
Smilow Cancer Hospital-Torrington Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Trumbull
Smilow Cancer Hospital Care Center-Trumbull
Contact: Site Public Contact
Email: canceranswers@yale.edu

Waterbury
Smilow Cancer Hospital-Waterbury Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Waterford
Smilow Cancer Hospital Care Center - Waterford
Contact: Site Public Contact
Email: canceranswers@yale.edu

FL
Jacksonville
Mayo Clinic in Florida
Contact: Site Public Contact

Tampa
Moffitt Cancer Center
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

Moffitt Cancer Center - McKinley Campus
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

Moffitt Cancer Center-International Plaza
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

GA
Atlanta
Emory University Hospital Midtown
Contact: Site Public Contact

IL
Chicago
Northwestern University
Contact: Site Public Contact
Email: cancer@northwestern.edu

KS
Kansas City
University of Kansas Cancer Center
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Overland Park
University of Kansas Cancer Center-Overland Park
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Westwood
University of Kansas Hospital-Westwood Cancer Center
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

LA
Baton Rouge
LSU Health Baton Rouge-North Clinic
Contact: Site Public Contact
Email: research@ololrmc.com

Our Lady of The Lake
Contact: Site Public Contact

Our Lady of the Lake Physicians Group - Medical Oncology
Contact: Site Public Contact
Email: research@ololrmc.com

MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Contact: Site Public Contact
Email: jhcccro@jhmi.edu

MI
Ann Arbor
University of Michigan Comprehensive Cancer Center
Contact: Site Public Contact

MN
Bemidji
Sanford Joe Lueken Cancer Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Rochester
Mayo Clinic in Rochester
Contact: Site Public Contact

MO
Creve Coeur
Siteman Cancer Center at West County Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Louis
Siteman Cancer Center-South County
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Washington University School of Medicine
Contact: Site Public Contact
Email: info@siteman.wustl.edu

NC
Durham
Duke University Medical Center
Contact: Site Public Contact

ND
Bismarck
Sanford Bismarck Medical Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Fargo
Sanford Broadway Medical Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Sanford Roger Maris Cancer Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

NE
Bellevue
Nebraska Medicine-Bellevue
Contact: Site Public Contact
Email: unmcrsa@unmc.edu

Omaha
Nebraska Medicine-Village Pointe
Contact: Site Public Contact

University of Nebraska Medical Center
Contact: Site Public Contact
Email: unmcrsa@unmc.edu

NY
Buffalo
Roswell Park Cancer Institute
Contact: Site Public Contact
Email: askroswell@roswellpark.org

Rochester
University of Rochester
Contact: Site Public Contact

OH
Columbus
Ohio State University Comprehensive Cancer Center
Contact: Site Public Contact
Email: Jamesline@osumc.edu

OK
Oklahoma City
University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

OR
Portland
Oregon Health and Science University
Contact: Site Public Contact
Email: trials@ohsu.edu

PA
Philadelphia
Fox Chase Cancer Center
Contact: Site Public Contact

Pennsylvania Hospital
Contact: Site Public Contact

University of Pennsylvania/Abramson Cancer Center
Contact: Site Public Contact

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Contact: Site Public Contact

RI
Westerly
Smilow Cancer Hospital Care Center - Westerly
Contact: Site Public Contact
Email: canceranswers@yale.edu

SD
Sioux Falls
Sanford Cancer Center Oncology Clinic
Contact: Site Public Contact
Email: OncologyClinicTrialsSF@sanfordhealth.org

Sanford USD Medical Center - Sioux Falls
Contact: Site Public Contact
Email: OncologyClinicalTrialsSF@SanfordHealth.org

TX
Houston
M D Anderson Cancer Center
Contact: Site Public Contact
Email: askmdanderson@mdanderson.org

UT
Salt Lake City
Huntsman Cancer Institute/University of Utah
Contact: Site Public Contact
Email: cancerinfo@hci.utah.edu

VA
Mechanicsville
VCU Massey Cancer Center at Hanover Medical Park
Contact: Site Public Contact
Email: CTOclinops@vcu.edu

Richmond
VCU Massey Cancer Center at Stony Point
Contact: Site Public Contact
Email: ctoclinops@vcu.edu

Virginia Commonwealth University/Massey Cancer Center
Contact: Site Public Contact
Email: CTOclinops@vcu.edu

Roanoke
Carilion Roanoke Memorial Hospital
Contact: Site Public Contact

South Hill
VCU Community Memorial Health Center
Contact: Site Public Contact
Email: nemer.elmouallem@vcuhealth.org

WI
Milwaukee
Medical College of Wisconsin
Contact: Site Public Contact

PRIMARY OBJECTIVE:
I. To assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS) patients as measured by disease free survival.

SECONDARY OBJECTIVES:
I. To assess whether there is a difference in the overall survival, recurrence free survival, distant metastases free survival, cumulative incidence of local recurrences and cumulative incidence of distant metastases between patients undergoing curative-intent surgery alone and those undergoing preoperative chemotherapy followed by curative intent surgery.
II. To assess tumor response in patients undergoing preoperative chemotherapy.
III. To assess the toxicity profile of preoperative chemotherapy given as "neoadjuvant" treatment to curative intent surgery in patients with retroperitoneal sarcoma (RPS), and of surgery alone.
IV. To assess whether there is a difference in quality of life between patients undergoing curative intent surgery alone and those undergoing preoperative chemotherapy followed by curative intent surgery.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo surgery on study. Patients also undergo collection of blood samples throughout the study and undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) at screening and follow up.

ARM II: Patients receive doxorubicin (or equivalent epirubicin) IV bolus infusion on day 1 with ifosfamide IV over 4 hours on days 1-3 or dacarbazine IV over 15-30 minutes on days 1-4. Cycles repeat every 21 days for 3 cycles and then patients undergo surgery on study. Patients also undergo collection of blood samples and undergo CT and/or MRI throughout the study.

After completion of study treatment, patients are followed up at 12, 18, 24, 36 and 48 weeks and every 4 months until month 24 after randomization. After 24 months, patients are followed every 6 months until occurrence of recurrence or death.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


This trial is sponsored by the European Organisation for Research and Treatment of Cancer - EORTC. The ECOG-ACRIN Cancer Research Group is collaborating in the trial with funding from the National Cancer Institute through its National Clinical Trials Network.

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EA7211 / STRASS 2 Home Page

ECOG-ACRIN Cancer Research Group