A randomized phase III study of neoadjuvant chemotherapy followed by surgery versus surgery alone for patients with High Risk RetroPeritoneal Sarcoma (STRASS 2)
S
Samantha Armstrong
Primary Investigator
Enrolling By Invitation
18 years - 100 years
All
Phase
3
4 Locations
Brief description of study
What is the purpose of this study?
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.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office
Email: iutrials@iu.edu
Phone: (317) 278-5632</div>
Detailed description of study
What will happen during the study?
After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.
Standard arm:
- Large en-bloc curative-intent surgery within 4 weeks following randomization- Experimental 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
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Retroperitoneal Sarcoma, Liposarcoma, Leiomyosarcoma, Cancer
-
Age: 18 years - 100 years
-
Gender: All
Inclusion Criteria:
- Histologicallyven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
- LMS:
- Any grade LMS can be included
- Minimum size of LMS tumor should be 5 cm
- LPS:
- Diagnosishould 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 (Fédération 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)
- Representatived, 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
- Resectableumor: 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)
- Patientust 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 allowedCT thorax + MRI abdomen & pelvis.
- ≥ 18 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
- Womenhild bearing potential (WOCBP) must have a negative serum pregnancywithin 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.
Ausal 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
- Sexualbstinence (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.
- Beforegistration/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
- Previouswith maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² 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.
- Othervasive 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
Updated on
10 Apr 2025.
Study ID: CTO-EA7211, 23092
Please visit our main page to search for other studies you may be interested in.
If you need help finding a study or have any questions, please contact us at inhealth@iu.edu
