A study to test the effect of chemotherapy before surgery compared to surgery alone in patients with high risk retroperitoneal sarcoma
- Conditions
- Primary high risk leiomyosarcoma or Liposarcoma of retroperitoneal space or infra-peritoneal spaces of pelvisTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003543-30-IT
- Lead Sponsor
- EORTC AISBL/IVZW
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
• 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 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 no necrosis on the biopsy but clear necrosis on imaging. 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
• ASA score < 3
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
• WOCBP in both arms should use higly 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, as defined below:
- With female partners of childbearing potential, men must remain abstinent* or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for 6 months after the last dose of chemotherapy. Men must refrain from donating sperm during this same period.
- With pregnant female partners, men must remain abstinent* or use a condom during the treatment period and for 28 days after the last dose of chemotherapy to avoid exposing the embryo.
• 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 ICH/GCP, and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1
• 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 pateints 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
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method