rEECur: International Randomised Controlled Trial of Chemotherapy for the Treatment of Recurrent and Primary Refractory Ewing Sarcoma

Trial details

Who runs it

The University Of Birmingham

Trial code

EU 2024-516078-31-00

Record updated

2024. december 4.

Original description

The objectives of the study are to compare systemic anti-cancer therapy regimens in recurrent/refractory ES in order to identify the best one with respect to efficacy (imaging response and survival), toxicity and acceptability to patients.Read full original descriptionShow less

The objectives of the study are to compare systemic anti-cancer therapy regimens in recurrent/refractory ES in order to identify the best one with respect to efficacy (imaging response and survival), toxicity and acceptability to patients.

Inclusion: Histologically confirmed Ewing or Ewing-like sarcoma of the bone or soft tissues. Histological confirmation either at initial diagnosis or disease progression; Patient agrees to use effective contraception during therapy and for 12 months after last trial treatment, where applicable; For IFOS/IFOS-L randomisation only: Adequate liver function: bilirubin <3 x ULN and ALT or AST < 5 x ULN; For IFOS/IFOS-L randomisation only: Left ventricular ejection fraction ≥50% at baseline as determined by echocardiography; For IFOS/IFOS-L randomisation only: Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as: a. BP <95th percentile for sex, age, and height. Subjects >18 years of age should have BP ≤150/90 mm Hg at screening; For IFOS/IFOS-L randomisation only: Urine dipstick <2+ for proteinuria. If ≥2+ proteinuria on dipstick, a spot urine protein:creatinine ratio test must be < CTCAE grade 2 Proteinuria; Written informed consent from the patient and/or parent/legal guardian; Radiological evidence of disease progression during or after completion of first or any subsequent line of treatment; Age ≥ 2 years (* Trial sites in Austria will only recruit patients aged ≥2 years<30 years due to the conditional approval issued by their ethics committee); Eligible for randomisation between at least two open study arms; Adequate renal function defined as GFR ≥60 ml/min/1.73m2. If GFR is calculated and is <90 ml/min/1.73m2, an isotopic GFR should be performed to confirm adequate renal function; Patient assessed as medically fit to receive trial treatment; Date of planned randomisation within 4 weeks of baseline imaging; Documented negative pregnancy test for female patients of childbearing potential.

Exclusion: Any central neurotoxicity with previous ifosfamide treatment; For IFOS/IFOS-L randomisation only: Arterial Thromboembolism in previous 6 months; For IFOS/IFOS-L randomisation only: Gastrointestinal bleeding or active haemoptysis within previous 3 weeks; For IFOS/IFOS-L randomisation only: Major surgery within previous 3 weeks; For IFOS/IFOS-L randomisation only: Previous treatment with tyrosine kinase inhibitors; Previous randomisation into the rEECur trial; Patients who have previously received one of the trial regimens off-trial may not be randomised to receive that regimen again. Patients who have had ifosfamide during first line therapy may receive the IFOS or IFOS-L arm. There is no requirement for a minimum time between receiving first line ifosfamide and entry to rEECur; Cytotoxic chemotherapy or other investigational medicinal product (IMP) within previous two weeks; Radiotherapy to target lesion within previous six weeks; Pre-existing medical condition that would necessitate a dose modification during cycle 1 as described in section 7 of the protocol; For CE randomisation only: Carboplatin is contraindicated in patients with actively bleeding tumours. Therefore, patients with actively bleeding tumours are not eligible for the CE randomisation; For IFOS/IFOS-L randomisation only: History of aneurysm; For IFOS/IFOS-L randomisation only: Gastrointestinal or non-gastrointestinal fistula; Clinical evidence of nephrotic syndrome; For IFOS/IFOS-L randomisation only: Radiographic evidence of intratumoral cavitation, encasement, or invasion of a major blood vessel, or proximity to major blood vessels with potential risk of severe haemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy; Patients with a contraindication or hypersensitivity to any IMP may not be randomised to receive an arm that contains the contraindicated IMP; Absolute Neutrophil Count (ANC) <1.0 x 109/L or platelets <75 x 109/L; For IFOS/IFOS-L randomisation only: Clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval >480 msec); Follow-up not possible due to social, geographic or psychological reasons; Pregnant or breastfeeding women.

EU CTIS 2024-516078-31-00