Ewing SarcomaPhase 1REGO-INTER-EWINCT05830084
Phase Ib / Regorafenib With Conventional Chemotherapy/Newly Diagnosed Patients/ Multimetastatic Ewing Sarcoma
A Phase 1 study testing regorafenib tablet in people with Ewing Sarcoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 13 sites in 6 countries.
Trial summary
New drug efficacy in ES has been disappointing in the last decades and no new drugs have been successfully introduced up to now in front line treatment. Among the tested drugs, early clinical data suggest that strategies using multi-targeted tyrosine kinase inhibitors (TKI) with anti-angiogenic activities are among… Read more about this study
- Who is it for?
- Ages 2 to 50 years
- Conditions the study is for
- Ewing Sarcoma
- What is being tested?
- regorafenib tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 16 Jun 2023to Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
- Metastatic disease
- Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
- 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
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- 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
- Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) ≥50%) at baseline, as determined by echocardiography
- 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.
- No prior treatment for Ewing sarcoma other than surgery
- Negative pregnancy test for female patients of childbearing potential within 7 days prior to study registration.
- 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
- Subject must be able to swallow and retain oral medication.
- 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.
- Patients must be affiliated to a social security system or beneficiary of the same, as per local regulatory requirements (France only)
Who cannot join
- Localized tumor or metastatic disease to lung/pleura only.
- Contra-indication to the Ewing sarcoma standard multimodal treatment
- Pregnant or breastfeeding women or intending to become pregnant during the study.
- Follow-up not possible due to social, geographic or psychological reasons
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of oral drugs
- 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
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- Previous arterial or venous thromboembolisms Grade ≥ 3 per CTCAE v5.0
- Hypersensitivity to any active substance or to any excipients
- Radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation
- Major surgical procedure or significant traumatic injury within 28 days before starting study treatment
- Non-healing wound, ulcer or bone fracture.
- Uncontrolled systemic or local infection requiring systemic treatment
- Any anticoagulant therapy (risk of hemorrhage with Regorafenib)
- Interstitial lung disease with ongoing signs and symptoms.
- Known prior history of HBV, HCV, HIV
- Any other medical or other condition that, in the opinion of the investigator(s), would preclude the subject's participation in this clinical study
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
France5 sites
CHU Bordeaux
Bordeaux
Centre Oscar Lambret
Lille
centre Léon Bérard
Lyon
Institut Curie
Paris
Gustave Roussy
Villejuif, Île-de-France Region, 94805
Australia4 sites
Queensland Children's Hospital
Brisbane
Monash Children's Hospital
Clayton
Royal Children's Hospital
Parkville
Perth Children's Hospital
Perth, WA6009
About this study
Official title: Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma
New drug efficacy in ES has been disappointing in the last decades and no new drugs have been successfully introduced up to now in front line treatment. Among the tested drugs, early clinical data suggest that strategies using multi-targeted tyrosine kinase inhibitors (TKI) with anti-angiogenic activities are among the most efficient and may be beneficial in the treatment of patients with ES.
Several TKI have been and are currently being tested as single-agent in patients with relapsed/refractory ES with encouraging results in phase II trials. Regorafenib has shown promising activity in Ewing sarcoma relapse setting, Nevertheless, regorafenib has never been combined with the intensive chemotherapy VDC/IE schedule and therefore this combination needs to be evaluated in order to avoid dose reduction of the current standard treatment and hence its efficacy.
The current clinical trial has been therefore designed to test the feasibility of regorafenib with ES conventional chemotherapy. It consists of a phase Ib that will only recruit patients with multi-metastatic (other than lungs/pleura only) ES, that present the highest unmet medical need (2 year EFS: 33%, similar to patients with relapse/refractory ES).
Read the detailed description
All included patients will receive standard Ewing sarcoma (ES) treatment concomitant with regorafenib.
Standard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice).
Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy
Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated, starting at DL0:
- DL1: 82 mg/m^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D)
- DL0 (starting dose): 66 mg/m^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D)
- DL-1: 50 mg/m^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D) Regorafenib will be stopped 2 weeks before planned surgery of the primary tumor and reintroduced when adequate wound healing is obtained, concomitant with consolidation VC/IE chemotherapy.
Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy.
- Conditions
- Ewing Sarcoma
- Being tested
- regorafenib tablet
- Medical subject headings
- Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regorafenib tabletDrug
Regorafenib will be escalated/de-escalated, starting at DL0:
- DL1: 82 mg/m^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D)
- DL0 (starting dose): 66 mg/m^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D)
- DL-1: 50 mg/m^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D)
| Study group | Role | What they receive |
|---|---|---|
| Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy | Experimental | Standard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice).
Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated.
Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy. Receives: Drug: regorafenib tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Dose-Limiting Toxicities (DLT)
The dose-finding escalation will be driven by the occurrence of Dose-Limiting Toxicities (DLT), assessed over the first 28-day cycle (cycle 1), and defined as any of the following haematological and non-haematological events that occur during the DLT period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib:
- Any cardiac toxicity grade ≥ 3
- Any grade 3 or 4 (hematological or non-hematological) toxicity leading to delay of start of next course by > 7 days (i.e: starting > day 21).
- Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy.
- Any grade 3 or 4 toxicity resulting in discontinuation of the new combination
- Any grade 5 toxicity related to study treatment (death)
Measured: 28 days after the start of treatment
Secondary outcomes (2)
Overall Survival (OS)
Defined as the time from start of anti-cancer treatment to death, irrespective of the cause. Surviving patients will be censored at their last follow-up date
Measured: Until 18 months after inclusion of the last patient
Progression-Free Survival (PFS)
Defined as the time from start of anti-cancer treatment to first event, where an event is progression without complete remission, recurrence following complete remission or death.
Measured: Until 18 months after inclusion of the last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2023
- Study start16 Jun 2023
- Primary completionApr 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ewing SarcomaStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patient with Ewing Sarcoma male or female age ≥2 years and \<50 years (from second birthday to 49 years 364 days) who are assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib. Patients will benefit from the social security coverage in force in their country and will have received free and informed information allowing the collection of their consent.
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Pablo Berlanga, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05830084
- Sponsor's protocol ID
- 2022-002874-10
- Other IDs
- 2023-503322-39-00, 2022/3545, 2023
- Acronym
- REGO-INTER-EWI
- Status last verified
- Jan 2026
- First submitted
- 13 Apr 2023
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma
- ClinicalTrials.gov ID
- NCT05830084
- Acronym / sponsor ID
- REGO-INTER-EWI / 2022-002874-10
- Conditions
- Ewing Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 16 Jun 2023 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 26 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
New drug efficacy in ES has been disappointing in the last decades and no new drugs have been successfully introduced up to now in front line treatment. Among the tested drugs, early clinical data suggest that strategies using multi-targeted tyrosine kinase inhibitors (TKI) with anti-angiogenic activities are among the most efficient and may be beneficial in the treatment of patients with ES.
Several TKI have been and are currently being tested as single-agent in patients with relapsed/refractory ES with encouraging results in phase II trials. Regorafenib has shown promising activity in Ewing sarcoma relapse setting, Nevertheless, regorafenib has never been combined with the intensive chemotherapy VDC/IE schedule and therefore this combination needs to be evaluated in order to avoid dose reduction of the current standard treatment and hence its efficacy.
The current clinical trial has been therefore designed to test the feasibility of regorafenib with ES conventional chemotherapy. It consists of a phase Ib that will only recruit patients with multi-metastatic (other than lungs/pleura only) ES, that present the highest unmet medical need (2 year EFS: 33%, similar to patients with relapse/refractory ES).
Detailed description
All included patients will receive standard Ewing sarcoma (ES) treatment concomitant with regorafenib.
Standard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice).
Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy
Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated, starting at DL0:
- DL1: 82 mg/m^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D)
- DL0 (starting dose): 66 mg/m^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D)
- DL-1: 50 mg/m^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D) Regorafenib will be stopped 2 weeks before planned surgery of the primary tumor and reintroduced when adequate wound healing is obtained, concomitant with consolidation VC/IE chemotherapy.
Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patient with Ewing Sarcoma male or female age ≥2 years and <50 years (from second birthday to 49 years 364 days) who are assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib. Patients will benefit from the social security coverage in force in their country and will have received free and informed information allowing the collection of their consent.
| Arm | Type | Receives |
|---|---|---|
| Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy | Experimental | Drug: regorafenib tabletStandard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice). Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated. Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy. |
Who may qualify
- Ages
- 2 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- 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
- Metastatic disease
- Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
- Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib, including:
- Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) ≥50%) at baseline, as determined by echocardiography
Key exclusion criteria (16 listed)
- Localized tumor or metastatic disease to lung/pleura only.
- Contra-indication to the Ewing sarcoma standard multimodal treatment
- Pregnant or breastfeeding women or intending to become pregnant during the study.
- Follow-up not possible due to social, geographic or psychological reasons
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of oral drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| regorafenib tabletRegorafenib will be escalated/de-escalated, starting at DL0: * DL1: 82 mg/m^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D) * DL0 (starting dose): 66 mg/m^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D) * DL-1: 50 mg/m^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D) | Drug | Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy |
Primary outcome
Occurrence of Dose-Limiting Toxicities (DLT)
Time frame: 28 days after the start of treatment
The dose-finding escalation will be driven by the occurrence of Dose-Limiting Toxicities (DLT), assessed over the first 28-day cycle (cycle 1), and defined as any of the following haematological and non-haematological events that occur during the DLT period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib: * Any cardiac toxicity grade ≥ 3 * Any grade 3 or 4 (hematological or non-hematological) toxicity leading to delay of start of next course by > 7 days (i.e: starting > day 21). * Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy. * Any grade 3 or 4 toxicity resulting in discontinuation of the new combination * Any grade 5 toxicity related to study treatment (death)
2 secondary outcomes
Overall Survival (OS)
Time frame: Until 18 months after inclusion of the last patient
Progression-Free Survival (PFS)
Time frame: Until 18 months after inclusion of the last patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo Berlanga, MD principal investigator
Gustave Roussy, Cancer Campus, Grand Paris
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing regorafenib tablet in people with Ewing Sarcoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, Australia, Denmark, Italy, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Dose-Limiting Toxicities (DLT) (time frame: 28 days after the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.