Phase II Prospective Multicenter Study of High-Dose Treosulfan/Melphalan as Consolidation Treatment in Newly Diagnosed High-Risk and Very High-Risk Ewing Sarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Santobono Pausilipon Onlus

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medac Gesellschaft für klinische Spezialpräparate m.b.H.,

External identifiers

EU CT number

2024-518912-37-01

EudraCT number

2023-000169-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

• To evaluate the safety and tolerability of using Treosulfan/Melphalan in Ewing Sarcoma within a multimodal treatment strategy
• To determine the 3y-EFS in high-risk and very high-risk Ewing Sarcoma patients treated with Treosulfan/Melphalan as part of a risk-adapted multimodal treatment strategy

Secondary objectives 1

1. • To determine the 3y-OS in high-risk and very high-risk Ewing Sarcoma patients treated with Treosulfan/Melphalan as part of a risk-adapted multimodal treatment strategy

Conditions and MedDRA coding

Ewing Sarcoma

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Primary diagnosed and histologically confirmed, localized or metastatic, Ewing sarcoma (ES) of bone or soft tissue, or ‘Ewing-like’ sarcoma but negative for EWSR1 gene rearrangement;
2. Patients with disseminated ES are included if any of the following conditions are present: a) 0-5 bone lesions at age < 14 years; b) 0-1 bone lesion at age > 14 years; c) bone marrow (BM) involvement; d) Extraosseous metastases + BM involvement or + bone lesion(s) with the aforementioned age-cut-offs;
3. Informed consent signed by the patient and/or by the parents/legal guardian;
4. Age < 50 years. Paediatric patients (< 18 years old) must be treated in accredited centers for the treatment of paediatric cancer patients
5. Registration to the protocol ≤ 45 days from diagnostic biopsy/surgery
6. Karnofsky > 50% for participants > 16 years old or Lansky Play Score > 50% for paediatric participants ≤ 16 years old or ECOG ≤ 2 for adult participants;
7. Adequate bone marrow function, defined as: Peripheral absolute neutrophil count (ANC) > 0.75 ×10 9 /L • Haemoglobin > 8.0 g/dL (transfusion allowed) • Platelet count > 75 × 10 9 /L (transfusion allowed)
8. Adequate organ function (serum creatinine < 1.5 x upper limit of normal (ULN), calculated creatinine clearance > 60 ml/min as determined by Cockcroft-Gault or according to age and sex as determined by Schwartz’s Formula, serum bilirubin ≤ 1.5 × ULN, except for Gilbert’s Syndrome, serum lipase and amylase ≤ 1.5 × ULN, ALT and AST≤ 2.5 × ULN or ≤ 5.0 × ULN for patients with hepatic metastases, normal ventricular ejection function as LVEF > 50% and SF > 28%);
9. A negative pregnancy test before enrolment and once a month during therapy for female participants of potential childbearing; for patients sexually active, it is mandatory to use an effective contraception throughout the treatment and up to 6 months beyond its end. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

Exclusion criteria 7

1. The presence of > 5 bone lesions at age < 14 years or > 1 bone lesion at age > 14 years. Bone lesions must be confirmed by CT scan, MRI, PET scan or, in doubtful cases, by biopsy;
2. Presence of concomitant bone metastases + bone marrow involvement (at least one site positive for metastatic infiltration);
3. Prior or concurrent chemotherapy or radiotherapy;
4. Any other severe concomitant comorbiditiesthat, according to the opinion of the Investigator, makes the enrollment in the study inappropriate for the patient, in particular: o myocardial infarction/unstable angina/congestive heart failure within 6 months before enrollment, LVEF less than the lower limit of normal per local institutional standards, history of clinically significant atrial arrhythmia or any history of ventricular arrhythmia; o uncontrolled hypertension, according to age values (patients with hypertension should be under treatment on study entry to carry out blood pressure control); o cerebrovascular accident or transient ischemic attack within 6 months before enrollment, any history of peripheral arterial occlusive disease requiring revascularization, venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months before enrolment; o uncontrolled metabolic alterations (such as hypertriglyceridemia); o severe active uncontrolled infection; o history of bleeding disorder; o history of acute pancreatitis (within 1 year before study entry) or history of chronic pancreatitis; o history of alcohol abuse;
5. Second malignancy;
6. Pregnant or breastfeeding women;
7. Neuropsychiatric, social, geographic or severe family problems that make it difficult for the patient to participate in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Frequency, duration, and severity of Adverse Effects (AEs) and Serious Adverse Effects (SAEs) according to CTCAE v. 5.0 • Event-Free Survival at 36 months defined as the time from the start of chemotherapy to disease progression, relapse, second malignancies, death from treatment-related complications, or the last follow-up

Secondary endpoints 1

1. Overall Survival at 36 months defined as the time from the start of chemotherapy to death or the last follow-up

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Santobono Pausilipon Onlus

Sponsor organisation

Fondazione Santobono Pausilipon Onlus

Address

Via Teresa Ravaschieri 8

City

Naples

Postcode

80122

Country

Italy

Scientific contact point

Organisation

Fondazione Santobono Pausilipon Onlus

Contact name

Maria Grazia Pionelli

Public contact point

Organisation

Fondazione Santobono Pausilipon Onlus

Contact name

Maria Grazia Pionelli

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications