Surgery With Our Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma

  • STATUS
    Recruiting
  • End date
    Apr 21, 2028
  • participants needed
    250
  • sponsor
    European Organisation for Research and Treatment of Cancer - EORTC
Updated on 30 July 2021
cancer
systemic therapy
measurable disease
gilbert's syndrome
neutrophil count
EGFR
cancer chemotherapy
ifosfamide
tubal occlusion
liposarcoma
dedifferentiated liposarcoma
leiomyosarcoma

Summary

This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival.

After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.

Description

Standard arm:

  • Large en-bloc curative-intent surgery within 4 weeks following randomizationExperimental arm

Experimental arm:

  • 3 cycles of neoadjuvant chemotherapy starting within 2 weeks following randomization:
  • High grade LPS: ADM (doxorubicin) 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m3 Q3 weeks.
  • LMS: ADM 75 mg/m2 + DTIC (dacarbazine) 1 g/m2 Q3 weeks
  • re-assessment of operability
  • curative-intent surgery within 3-6 weeks of last cycle of chemotherapy

Details
Condition leiomyosarcoma, liposarcoma, Sarcoma, Retroperitoneal Sarcoma, Sarcoma (Pediatric), Soft Tissue Sarcoma
Treatment Surgery, Preoperative chemotherapy
Clinical Study IdentifierNCT04031677
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC
Last Modified on30 July 2021

Eligibility

Yes No Not Sure

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 of LMS can be included
Minimum size of LMS tumor should be 5 cm
LPS
Diagnosis 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 biopsy can be included when
The grade 2 DDLPS has an FNCLCC score=5 (Fdration Nationale des Centres de Lutte Contre Le Cancer), has no necrosis on the biopsy but clear necrosis on imaging
The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides must be available at baseline for histological central review
Unifocal tumor
Absence of extension through the sciatic notch or across the diaphragm
Resectable tumor: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcoma team. A patients 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 leiomyosarcoma towards the right atrium
Infiltration of multiple major organs like liver, pancreas and/or major vessels
Tumor not previously treated (no previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy)
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
years old (no upper age limit)
WHO (World Health Organization) performance status 2
Adequate haematological and organ function
Haematological: haemoglobin > 9.0 g/dL or 5.6 mmol/L, absolute neutrophils > 1.5 x 109/L, platelets > 100 x 109/L Note: Platelet transfusions is allowed to achieve these baseline values
Renal: estimated glomerular filtration rate (eGFR) > 50 ml/min/m2; No proteinuria CTCAE grade 2
Hepatic: Bilirubin 1.0 times upper limit of normal (1.0xULN) of institutional limits, ALT (alanine aminotransferase) and/or AST (aspartate transaminase) 1.5 x ULN. 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
Heart: 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 ECG without clinically relevant abnormalities
American Society of Anesthesiologist (ASA) score < 3
Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment or surgery
Note: a woman is considered of childbearing potential (WOCBP), i.e. fertile
following menarche and until becoming post menopausal unless permanently
sterile
Permanent sterilisation 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 months of amenorrhea, a single FSH measurement is
insufficient
Patients of childbearing / reproductive potential should use highly effective birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment or date of surgery. 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. Such methods include
Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
Intrauterine device (IUD)
Intrauterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Vasectomized partner
Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
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 registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria

Sarcoma originated from bone structure, abdominal or gynecological viscera
Metastatic disease
Tumors with extension through the sciatic notch or across the diaphragm
Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
Persistent myelosuppression
Myocardial infarction within the last 6 months
Uncontrolled cardiac arrhythmia
Previous treatment with maximum cumulative doses (450mg/m Doxorubicin or equivalent 900mg/m EpiADM) 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 presumably cured prostate cancer
Uncontrolled severe illness, infection,medical condition (including, uncontrolled diabetes or hypertension), 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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note