Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Chondrosarcoma

Chondroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

For adult patients (≥18 years old) : 160 mg/d once daily for the 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent .

For children Age ≥10 years to \<18 years old and BSA ≥1.30 m², regorafenib (82 mg/m²) once daily for the 3 weeks on/1 week off (without exceeding 160 mg/day) plus Best Supportive care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent.

Placebo plus BCS until progression (according to RECIST V1.1) intolerance or withdrawal of consent. Patients who have received placebo will receive open-label regorafenib after objective tumor progression.

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily until progression or unacceptable toxicity For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily until progression or unacceptable toxicity

Regorafenib

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily and switch to regorafenib after confirmed progression For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily and switch to regorafenib after confirmed progression

Placebo

Sabrina YARA

Elsa KALBACHER, MD

Antoine ITALIANO, MD

Corinne DELCAMBRE, MD

Alice HERVIEU, MD

Nicolas PENEL, MD

Jean Yves BLAY, MD PhD

François BERTUCCI, MD PhD

Florence DUFFAUD, MD PhD

Didier CUPISSOL, MD

Antoine THYSS, MD PhD

Pascaline BOUDOU-ROUQUETTE, MD

Sophie PIPERNO-NEUMANN, MD

Christophe PERRIN, MD

Emmanuelle BOMPAS, MD

Olivier COLLARS, MD

Christine CHEVREAU, MD

Helene VEGAS, MD

Maria RIOS, MD

Olivier MIR, MD

INDICATION:

Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas and either bone or soft tissue metastatic CIC-rearranged sarcomas

METHODOLOGY:

Randomized, placebo-controlled, multicentric, phase II study -This is a double-blind placebo-controlled trial, with 5 cohorts: cohort A: Osteosarcoma, cohort B: Ewing sarcoma, cohort C: Chondrosarcoma, cohort D : chondroma, cohort E: CIC-rearranged sarcoma. Cohort A, B and C will involve a total of 36 patients (24 Regorafenib + 12 placebo), cohort D a total of 24 evaluable patients (16 Regorafenib + 8 placebo) and cohort E will involve a total of 27 evaluable patients (18 Regorafenib + 9 placebo).

159 patients who meet the eligibility criteria will be randomly assigned in a 2:1 ratio to the following treatment groups :

The Arm A:

Regorafenib (160 mg/d) once daily for the 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent .

Patients receiving regorafenib who experience disease progression and for whom in the investigator opinion, treatment with regorafenib is providing clinical benefit, may continue the treatment following consultation with the study coordinator and the sponsor.

The Arm B:

Placebo plus BSC until progression (according to RECIST V1.1) intolerance or withdrawal of consent. Patients who have received placebo will receive open-label regorafenib after objective tumor progression.

Patients will be stratified at randomization according to histology .

A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

A Randomized Phase II, Placebo-controlled, Multicenter Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

Proportion of patients without disease progression at the defined timepoint after central radiological review (using RECIST 1.1)

from the date of randomization until the date of radiological progression or death whatever the cause (if death occurs before progression)

complete response (CR) or partial response (PR) according to RECIST 2009, version 1.1, for all cohorts, and CHOI criteria for chordoma

from the date of randomization until the date of death due to any cause

objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression

the proportion of patients without progression at 3 and 6 months post randomization

from date of randomization until the date of first observation of progression

ratio of time to PD under regorafenib to TTP under previous treatment

according to NCI-CTCAE V4-0 (National Cancer Institut Common Terminology Criteria for Adverse Events)

Progression Free Survival according to Choi criteria for Chordoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas	NCT02389244	Ewing Sarcomas Chondrosarcomas Osteosarcomas Chondroma CIC-Rearranged ...	Regorafenib Placebo	10 Years -	UNICANCER
A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas	NCT02389244	Ewing Sarcomas Chondrosarcomas Osteosarcomas Chondroma CIC-Rearranged ...	Regorafenib Placebo	10 Years -	UNICANCER

Spots Global Cancer Trial Database for ewing sarcomas