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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

INDICATION:

Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas


Detailed Summary:

METHODOLOGY:

Randomized, placebo-controlled, multicentric, phase II study -This is a double-blind placebo-controlled trial, with 4 cohort: cohort A: Osteosarcoma cohort B: Ewing sarcoma cohort C: Chondrosarcoma cohort D : chondroma. Cohort A, B and C will involve a total of 36 patients (24 Regorafenib + 12 placebo). And cohort D a total of 24 evaluable patients (16 Regorafenib + 8 placebo) 132 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 .


Sponsor: UNICANCER

Current Primary Outcome: The primary efficacy endpoint is progression free survival (PFS) [defined using RECIST 1.1] after central radiological review [ Time Frame: expected average duration of 3 months ]

from the date of randomization until the date of radiological progression or death whatever the cause


Original Primary Outcome: The primary efficacy endpoint is PFS [defined using RECIST 1.1] after central radiological review [ Time Frame: expected average duration of 3 months ]

from the date of randomization until the date of radiological progression or death whatever the cause


Current Secondary Outcome:

  • Objective response rate [ Time Frame: 6 months ]
    complete response (CR) or partial response (PR) according to RECIST 2009, version 1.1, for all cohorts, and CHOI criteria for chordoma
  • Disease control rate at 6 months [ Time Frame: 6 months ]
    from the date of randomization until the date of death due to any cause
  • Overall survival [ Time Frame: the time from the date of randomization until the date of death due to any cause (up to 6 months) ]
  • Duration of response [ Time Frame: expected average duration of 6 months ]
    objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression
  • Progression-free rate at 3 and 6 months [ Time Frame: at 3 and 6 months ]
  • Time to progression [ Time Frame: from date of randomization until the date of first observation of progression (up to 6 months) ]
  • Growth Modulation Index defined as ratio of time to progressive disease (PD) under regorafenib to time to progression (TTP) under previous treatment [ Time Frame: time to PD under regorafenib to TTP under previous treatment (up to 6 months) ]
  • Toxicity according to NCI-CTCAE V4-0 [ Time Frame: expected average duration of 6 months ]
    according to NCI-CTCAE V4-0 (National Cancer Institut Common Terminology Criteria for Adverse Events)
  • Pain assessment using Visual analog scale (VAS), DN4 scale (Neuropathic Pain Diagnostic Questionnaire) and NPSI scale (Neuropathic Pain Symptom Inventory) [ Time Frame: expected average duration of 6 months ]
    for chordomas cohort only
  • PFS [ Time Frame: from date of randomization until the date of first observation of progression (up to 6 months) ]
    Progression Free Survival according to Choi criteria for Chordoma


Original Secondary Outcome:

  • Objective response rate [ Time Frame: 6 months ]
  • Disease control rate at 6 months [ Time Frame: 6 months ]
    from the date of randomization until the date of death due to any cause
  • Overall survival [ Time Frame: the time from the date of randomization until the date of death due to any cause (up to 6 months) ]
  • Duration of response [ Time Frame: expected average duration of 6 months ]
    objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression
  • Progression-free rate at 3 and 6 months [ Time Frame: at 3 and 6 months ]
  • Time to progression [ Time Frame: from date of randomization until the date of first observation of progression (up to 6 months) ]
  • Growth Modulation Index defined as ratio of time to PD under regorafenib to TTP under previous treatment [ Time Frame: time to PD under regorafenib to TTP under previous treatment (up to 6 months) ]


Information By: UNICANCER

Dates:
Date Received: February 9, 2015
Date Started: September 2014
Date Completion: March 2020
Last Updated: June 21, 2016
Last Verified: June 2016