Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma (STRASS2)

• Procedure: Surgery
• Drug: Preoperative chemotherapy

Inclusion Criteria:

• Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
• LMS:
  • Any gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells LMS can be included
  • Minimum size of LMS tumor should be 5 cm
• LPS:
  • Diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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 biopsyremoval of a section of tissue to analyse for cancer cells can be included when:
    • The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs), and clear necrosis on imagingtests that create detailed images of areas inside the body (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 tumoura tissue mass that forms from groups of unhealthy cells
  • Resectable tumour: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcomacancer arising from bones and/or soft tissue team. A patient is not considered resectable when the expectation is that only an R2 resectionsurgical removal of tissue or part/all of an organ is feasible.
  • Criteria for non-resectability are:
  • Involvement of the superior mesenteric arterya blood vessel that carries oxygenated blood from the heart to the rest of the body, aorta, coeliac trunk and/or portal veina blood vessel that carries deoxygenated blood to the heart to get oxygen
  • 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, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation and or major vessels
  • Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. CT thorax abdomenstomach, stomach area, belly 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 tissuea group of cells that work together to perform a function for central pathologythe study of disease 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 bloodthe red bodily fluid that transports oxygen and other nutrients around the body 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 hysterectomycomplete or partial removal of the uterus, bilateralaffecting both sides salpingectomyremoval of one (unilateral) or both (bilateral) fallopian tubes and bilateral oophorectomy.

A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body (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 dosethe amount of medication taken 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 consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. must be given according to ICH/GCP, and national/local regulations.