A study to test the effect of chemotherapy before surgery compared to surgery alone in patients with high risk retroperitoneal sarcoma

Phase 1

• Conditions: Primary high risk leiomyosarcoma or Liposarcoma ofretroperitoneal space or infra-peritoneal spaces of pelvis; MedDRA version: 20.0Level: PTClassification code 10073135Term: Dedifferentiated liposarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10024189Term: LeiomyosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003543-30-GB
• Lead Sponsor: European Organisation for Research and Treatment of Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-15
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• 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
• American Society of Anesthesiologist (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 th

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 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