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

European Organisation for Research and Treatment of Cancer - EORTC164 sites in 6 countries250 target enrollmentJanuary 20, 2021

ConditionsRetroperitoneal Sarcoma Liposarcoma Leiomyosarcoma

InterventionsSurgery Preoperative chemotherapy

DrugsPreoperative chemotherapy

Overview

Phase: Phase 3
Intervention: Surgery
Conditions: Retroperitoneal Sarcoma
Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Enrollment: 250
Locations: 164
Primary Endpoint: Disease free survival
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Detailed Description

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

Registry

clinicaltrials.gov

Start Date

January 20, 2021

End Date

April 21, 2028

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Inclusion Criteria:
•Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
•Any grade LMS can be included
•Minimum size of LMS tumor should be 5 cm
•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 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy).
•The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
•Unifocal tumour

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.
•Note: 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.

Arms & Interventions

Standard arm

Surgery alone

Intervention: Surgery

Experimental arm

Preoperative chemotherapy and surgery

Intervention: Preoperative chemotherapy

Outcomes

Primary Outcomes

Disease free survival

Time Frame: 7 years from first patient in

Disease free survival will be measured from the date of randomization (as reference) to the date of recurrence or death, whichever occurs first.

Secondary Outcomes

Overall survival (OS)(8 years from first patient in)
Recurrence free survival(8 years from first patient in)
Distant metastases free survival(8 years from first patient in)
Cumulative incidence of local recurrences(8 years from first patient in)
Cumulative incidence of distant metastases(8 years from first patient in)
Radiological response to neoadjuvant chemotherapy according to RECIST(8 years from first patient in)
Radiological response to neoadjuvant chemotherapy according to CHOI(8 years from first patient in)
Safety and toxicity of neoadjuvant chemotherapy(8 years from first patient in)
Late complications(8 years from first patient in)
Health utility, calculated from the collected patient-reported HRQoL data and patient demographics economics.(8 years from first patient in)
Pathological response(8 years from first patient in)
Health-Related Quality of life (EORTC QLQ-C30 + Item list from QLQ-STO22)(8 years from first patient in)
Perioperative complications(8 years from first patient in)