Combining regorafenib with standard chemotherapy for Ewing sarcoma

Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma

This study is testing if adding a new drug called regorafenib to standard chemotherapy can help people with newly diagnosed Ewing sarcoma do better in their treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 2 Years to 50 Years
• Sex: All
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 6 sites (Perth and 5 other locations)
• Trial ID: NCT05830084 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the feasibility and efficacy of combining regorafenib, a multi-targeted tyrosine kinase inhibitor, with standard chemotherapy for patients with newly diagnosed multimetastatic Ewing sarcoma. Participants will receive the conventional treatment regimen of induction chemotherapy followed by consolidation chemotherapy, with regorafenib administered concurrently. The study will assess the safety and tolerability of this combination, as well as its potential to enhance treatment outcomes without reducing the effectiveness of standard chemotherapy. The trial will also explore dose adjustments of regorafenib based on patient response and tolerability.

Who should consider this trial

Good fit: Ideal candidates are patients aged 2 to 49 years with histologically confirmed multimetastatic Ewing sarcoma.

Not a fit: Patients with localized Ewing sarcoma or those who are not medically fit to receive chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with Ewing sarcoma by enhancing the efficacy of standard chemotherapy.

How similar studies have performed: While other studies have explored the use of regorafenib in Ewing sarcoma, this specific combination with standard chemotherapy is novel and has not been previously tested.

Eligibility criteria

Inclusion Criteria:

1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or round cell sarcomas which are 'Ewing's-like' but negative for EWSR1 gene rearrangement
2. Metastatic disease
3. Age ≥2 years and \<50 years (from second birthday to 49 years 364 days)
4. Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib, including:

   * Absolute Neutrophil Count (ANC) ≥ 0.75x10\^9/L, platelets ≥ 75x10\^9/L.
   * Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN
   * Bilirubin ≤ 2×ULN
   * Creatinine \< 2x ULN or creatinine clearance \>60 ml/min/1.73 m\^2
   * International normalized ratio (INR)/ Partial thromboplastin time (PTT). INR and PTT ≤ 1.5 x ULN. INR \& PTT ≤ 1.5xULN
5. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) ≥50%) at baseline, as determined by echocardiography
6. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as: a BP \<95th percentile for sex, age, and height at screening (as per National Heart Lung and Blood Institute \[NHLBI\] guidelines) and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1. Patients \>18 years old should have BP ≤ 150/90 mmHg.
7. No prior treatment for Ewing sarcoma other than surgery
8. Negative pregnancy test for female patients of childbearing potential within 7 days prior to study registration.
9. Patient agrees to use highly effective contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where applicable
10. Subject must be able to swallow and retain oral medication.
11. Written informed consent from the patient and/or the parent/legal guardian, according to local, regional or national regulation prior to any study specific procedures.
12. Patients must be affiliated to a social security system or beneficiary of the same, as per local regulatory requirements (France only)

Exclusion Criteria:

1. Localized tumor or metastatic disease to lung/pleura only.
2. Contra-indication to the Ewing sarcoma standard multimodal treatment
3. Pregnant or breastfeeding women or intending to become pregnant during the study.
4. Follow-up not possible due to social, geographic or psychological reasons
5. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of oral drugs
6. A clinically significant ECG abnormality, including a marked prolonged QTcF interval (eg, a repeated demonstration of a QTcF interval \>480 msec) Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality, unstable angina, active coronary artery disease and myocardial infarction within 6 months before randomization.) Uncontrolled hypertension (systolic pressure \>150 mmHg or diastolic pressure \> 90 mmHg on repeated measurement) despite optimal medical management
7. Previous arterial or venous thromboembolisms Grade ≥ 3 per CTCAE v5.0
8. Hypersensitivity to any active substance or to any excipients
9. Radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation
10. Major surgical procedure or significant traumatic injury within 28 days before starting study treatment
11. Non-healing wound, ulcer or bone fracture.
12. Uncontrolled systemic or local infection requiring systemic treatment
13. Any anticoagulant therapy (risk of hemorrhage with Regorafenib)
14. Interstitial lung disease with ongoing signs and symptoms.

Where this trial is running

Perth and 5 other locations

• Perth Children's Hospital — Perth, Australia (Recruiting)
• Rigshospitalet — Copenhagen, Denmark (Not_yet_recruiting)
• Gustave Roussy — Villejuif, Ile De France, France (Recruiting)
• Istituto Nazionale dei Tumori — Milan, Italy (Not_yet_recruiting)
• Princess Máxima Center — Utrecht, Netherlands (Recruiting)
• Vall d'Hebron University Hospital — Barcelona, Spain (Not_yet_recruiting)

Study contacts

• Principal investigator: Pablo Berlanga, MD — Gustave Roussy, Cancer Campus, Grand Paris
• Study coordinator: Pablo Berlanga, MD, PhD

Conditions Bone Cancer