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Phase Ib / Regorafenib With Conventional Chemotherapy/Newly Diagnosed Patients/ 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).
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 2 and older
Healthy volunteers accepted : Yes
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-06-16
Primary completion: 2026-06-01
Study completion finish: 2026-06-01
Study type
TREATMENT
Phase
PHASE1
Trial ID
NCT05830084
Intervention or treatment
DRUG: regorafenib tablet
Conditions
- • Bone Cancer
Find a site
Closest Location:
Perth Children's Hospital
Research sites nearby
Select from list below to view details:
Perth Children's Hospital
Perth, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy
| DRUG: regorafenib tablet
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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) | 28 days after the start of treatment |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
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 | 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. | Until 18 months after inclusion of the last patient |
Frequently Asked Questions
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