Primary high risk leiomyosarcoma or Liposarcoma of retroperitoneal space or infra-peritoneal spaces of pelvis MedDRA version: 20.0 Level: PT Classification code 10073135 Term: Dedifferentiated liposarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10024189 Term: Leiomyosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
European Organisation for Research and Treatment of Cancer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis. - LMS: Any grade and size > 5 cm - LPS (diagnosis based on MDM2 and CDK4 expression on IHC; additional proof of MDM2 amplification is highly recommended but not mandatory): * Grade 3 DDLPS OR * Confirmed grade 2 DDLPS on biopsy only if: 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 tumour • Resectable tumour: 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 (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 performance status = 2 • Adequate haematological and organ function assessed within 21 days prior to randomization • American Society of Anesthesiologist (ASA) score =65 years) yes F.1.3.1 Number of subjects for this age range 87
Exclusion criteria
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 • 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 = 6 prostate 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of patients with high risk de-differentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS) as measured by disease-free survival.;Secondary Objective: • 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 • To assess tumour response in patients undergoing preoperative chemotherapy • To assess the toxicity profile of preoperative chemotherapy given as "neoadjuvant" treatment to curative intent surgery in patients with high risk retroperitoneal (RPS) and of surgery alone • 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;Primary end point(s): Disease free survival (which includes as events: distant progression on neoadjuvant treatment, local progression if not followed by R0/R1 surgery, non-operable tumours, local recurrence and/or distant metastases, R2 and death);Timepoint(s) of evaluation of this end point: Disease free survival will be evaluated 4 years after FPI (first interim look for futility), 5 years after FPI (second interim look for futility) and 7 years after FPI (final analysis) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival • Recurrence free survival • Distant metastases free survival • Cumulative incidence of local recurrences • Cumulative incidence of distant metastases • Radiological response to neoadjuvant chemotherapy according to RECIST • Radiological response to neoadjuvant chemotherapy according to CHOI • Pathological response • Safety and toxicity of neoadjuvant chemotherapy • Perioperative complications • Late complications • Health-Related Quality of life (EORTC QLQ-C30 + Item list from QLQ-STO22);Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated at time of the final primary endpoint analysis: 7 years after FPI. A long term overall survival analysis will also be performed at later timepoint after EoT. | — |
Countries
Australia, Canada, Cyprus, Czechia, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Poland, Slovakia, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs Department
European Organisation for the Research and Treatment of Cancer
Outcome results
None listed