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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05830084


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT05830084
Ethics application status
Date submitted
13/04/2023
Date registered
26/04/2023
Date last updated
11/05/2023

Titles & IDs
Public title
Phase Ib / Regorafenib With Conventional Chemotherapy/Newly Diagnosed Patients/ Multimetastatic Ewing Sarcoma
Scientific title
Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma
Secondary ID [1] 0 0
2022/3545
Secondary ID [2] 0 0
2022-002874-10
Universal Trial Number (UTN)
Trial acronym
REGO-EWING
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - regorafenib tablet

Experimental: Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy - 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.


Treatment: Drugs: regorafenib tablet
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Dose-Limiting Toxicities (DLT)
Timepoint [1] 0 0
28 days after the start of treatment
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Until 18 months after inclusion of the last patient
Secondary outcome [2] 0 0
Progression-Free Survival (PFS)
Timepoint [2] 0 0
Until 18 months after inclusion of the last patient

Eligibility
Key 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)
Minimum age
2 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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. Interstitial lung disease with ongoing signs and symptoms.
13. Any other medical or other condition that, in the opinion of the investigator(s), would preclude the subject's participation in this clinical study

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
27/03/2026
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Ile De France

Funding & Sponsors
Primary sponsor type
Other
Name
Gustave Roussy, Cancer Campus, Grand Paris
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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 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).
Trial website
https://clinicaltrials.gov/study/NCT05830084
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Pablo Berlanga, MD
Address 0 0
Gustave Roussy, Cancer Campus, Grand Paris
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pablo Berlanga, MD
Address 0 0
Country 0 0
Phone 0 0
+33 (0)1 42 11 41 67
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05830084

Additional trial details provided through ANZCTR
Accrual to date
4
Recruiting in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 164
Queensland Children's Hospital
Recruitment hospital [2] 165
Perth Children's Hospital
Recruitment hospital [3] 166
Monash Children’s Hospital
Recruitment hospital [4] 167
Chris O’Brien Lifehouse
Recruitment postcode(s) [1] 164
4101
Recruitment postcode(s) [2] 165
6009
Recruitment postcode(s) [3] 166
3168
Recruitment postcode(s) [4] 167
2050
Funding & Sponsors
Funding source category [1] 91
Charities/Societies/Foundations
Name [1] 91
The Australian Organisation for Young People Living with Cancer (Canteen)
Address [1] 91
75 King St, Newtown NSW 2042 Australia
Country [1] 91
Australia
Funding source category [2] 92
Government body
Name [2] 92
MRFF, Australian Department of Health
Address [2] 92
Department of Health GPO Box 9848 Canberra ACT 2601 Australia
Country [2] 92
Australia
Funding source category [3] 93
Charities/Societies/Foundations
Name [3] 93
The Kid's Cancer Project
Address [3] 93
Suite 1, Level 1/789 Botany Rd, Rosebery NSW 2018
Country [3] 93
Australia
Funding source category [4] 94
Other Collaborative groups
Name [4] 94
Australian and New Zealand Sarcoma Association
Address [4] 94
VCCC Level 1 305 Grattan Street Melbourne Victoria 3000 Australia
Country [4] 94
Australia
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australia and New Zealand Children's Haematology and Oncology Group (ANZCHOG)
Primary sponsor address
27-31 Wright St, Clayton VIC 3168
Primary sponsor country
Australia
Other collaborator category [1] 95
Hospital
Name [1] 95
Gustave Roussy
Address [1] 95
114 Rue Edouard Vaillant, 94805 Villejuif, France
Country [1] 95
France
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 68
The Child and Adolescent Health Service Human Research Ethics Committee
Address [1] 68
15 Hospital Avenue Nedlands WA 6009
Country [1] 68
Australia
Date submitted for ethics approval [1] 68
11/07/2023
Approval date [1] 68
14/08/2023
Ethics approval number [1] 68
RGS0000006256
 
Public notes

Contacts
Principal investigator
Title 413 0
A/Prof
Name 413 0
Marianne Phillips
Address 413 0
Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
Country 413 0
Australia
Phone 413 0
+618 6456 4427
Fax 413 0
Email 413 0
[email protected]
Contact person for public queries
Title 414 0
A/Prof
Name 414 0
Marianne Phillips
Address 414 0
Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
Country 414 0
Australia
Phone 414 0
+618 6456 4427
Fax 414 0
Email 414 0
[email protected]
Contact person for scientific queries
Title 415 0
A/Prof
Name 415 0
Marianne Phillips
Address 415 0
Clinic H, Room H14 Locked Bag 2010, Nedlands WA 6909
Country 415 0
Australia
Phone 415 0
+618 6456 4427
Fax 415 0
Email 415 0
[email protected]