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Official Title

A Randomized Phase III Study of Neoadjuvant Chemotherapy Followed by Surgery Versus Surgery Alone for Patients With High Risk RetroPeritoneal Sarcoma (RPS)

Phase
Phase 3
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Enrollment
250
Timeline
Jan 2021 → Apr 2028
About 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. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.

Eligibility Criteria

Inclusion Criteria

  • 1Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
  • 2LMS:
  • 3Any grade LMS can be included
  • 4Minimum size of LMS tumor should be 5 cm
  • 5LPS:
  • 6Diagnosis 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.
  • 7All grade 3 DDLPS can be included.
  • 8DDLPS with confirmed grade 2 on biopsy can be included when:
  • 9The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy).
  • 10The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
  • 11Unifocal tumour
  • 12Resectable tumour: 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 patient is not considered resectable when the expectation is that only an R2 resection is feasible.
  • 13Criteria for non-resectability are:
  • 14Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein
  • 15Involvement of bone
  • 16Growth into the spinal canal
  • 17Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium
  • 18Infiltration of multiple major organs like liver, pancreas and or major vessels
  • 19Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. 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
  • 20Collection of tumour tissue for central pathology review is mandatory.
  • 21For patients with LMS: if there is not enough tissue for assessing the grading, this is acceptable.
  • 22If tumour tissue is not available for the central pathology review, patient will not be eligible.
  • 23If the biopsy was not done or the FFPE of the biopsy not available but at least 10 unstained slides or one pathological block are available for the central review, that will be considered as acceptable.
  • 24For the biopsy if fine needle aspiration (FNA) is performed instead of core needle biopsy (CNB) recommended by the standard guidelines, please contact the EORTC medical monitors for further evaluation.
  • 25Collection of tumour tissue and blood samples for translational research is mandatory.
  • 26In case there is not enough tissue for TR, a new biopsy is not required and if the patient fulfils all other eligibility criteria, he/she will be eligible.
  • 27If the blood samples are not collected, patient will not be eligible.
  • 28If the patient refuses the collection of biomaterial for TR, patient will not be eligible even if he/she fulfils all other eligibility criteria
  • 29≥ 18 years old (no upper age limit)
  • 30WHO performance status ≤ 2
  • 31Adequate haematological and organ function
  • 32American Society of Anaesthesiologist (ASA) score \< 3
  • 33Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
  • 34Note: a woman is considered of childbearing potential, i.e., fertile, if she is following menarche. She remains of childbearing potential until she becomes post-menopausal or permanently sterile.Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • 35A 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 consecutive months without menses, a single FSH measurement is insufficient.
  • 36WOCBP in both arms should use highly 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.
  • 37For men in the experimental arm: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
  • 38Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6months after the last study treatment.
  • 39Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
  • 40Patients who meet all eligibility criteria of STRASS 2 but do not consent to randomization or are not enrolled for any other reason.
  • 41Patients enrolled in a Registry collecting data on primary RPS patients in the centres participating in STRASS 2 (e.g., RESAR) and who satisfy the above criteria.
  • 42Selection criteria for preferences for neoadjuvant chemotherapy in STRASS 2 substudy
  • 43All patients recruited to STRASS 2 in participating centres (Australia +/- international sites) that are able to read, comprehend and write in English at a sufficient level to complete study materials.

Exclusion Criteria

  • 1Sarcoma originating from bone structure, abdominal or gynecological viscera
  • 2Extension through the sciatic notch or across the diaphragm
  • 3Metastatic disease
  • 4Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour
  • 5Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
  • 6Congestive heart failure
  • 7Angina pectoris
  • 8Myocardial infarction within 1 year before randomization
  • 9Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy.
  • 10Note: in case of high blood pressure: 1) initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 2) blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 150/90mmHg in order for a patient to be eligible for the study.
  • 11Uncontrolled cardiac arrhythmia
  • 12Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
  • 13Active and uncontrolled infections
  • 14Vaccination with live vaccines within 30 days prior to study entry
  • 15Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
  • 16Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer.
  • 17Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum.
  • 18Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method.
  • 19Any 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
  • 20Known contraindication to imaging tracer and to MRI
  • 21Selection criteria for STREXIT 2

Locations

149 sites participating in this study

Emory University Hospital Midtown

Atlanta, Georgia 30308

Recruiting

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

Recruiting

City of Hope Comprehensive Cancer Center

Duarte, California 91010

Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →