check_circleStudy Completed

Pediatric oncology

A Phase I dose finding study in children with solid tumors recurrent or refractory to standard therapy

Trial purpose

Dose escalation phase of the study :
To define the safety profile, maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of regorafenib administered orally as a single agent in a 3-weeks-on/1- week-off schedule in repeating cycles of 28 days in pediatric subjects with solid malignant tumors recurrent or refractory to standard therapy. To characterize the pharmacokinetics (PK) of regorafenib
The dose escalation phase of the study has been completed.
Expansion phase:
To define the safety profile, MTD and the RP2D of regorafenib administered orally in combination with
backbone chemotherapy (vincristine and irinotecan) at relapse in pediatric subjects with rhabdomyosarcoma (RMS) and other solid malignant tumors recurrent or refractory to standard therapy.

Key Participants Requirements

Sex

Both

Age

6 - 18 Years

Trial summary

Enrollment Goal
62
Trial Dates
April 2014 - March 2024
Phase
Phase 1
Could I Receive a placebo
No
Products
Stivarga (Regorafenib, BAY73-4506)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Milano, 20133, Italy
Active, not recruiting
Sutton, SM2 5PT, United Kingdom
Completed
VILLEJUIF CEDEX, 94805, France
Completed
lyon, 69008, France
Completed
Paris, 75248, France
Completed
Birmingham, B4 6NH, United Kingdom
Active, not recruiting
Newcastle Upon Tyne, NE1 4LP, United Kingdom
Completed
Manchester, M13 9WL, United Kingdom
Withdrawn
Leeds, LS1 3EX, United Kingdom
Withdrawn
Glasgow, G51 4TF, United Kingdom
Completed
Genova, 16147, Italy
Withdrawn
Roma, 00168, Italy
Withdrawn
Barcelona, 08035, Spain
Completed
Valencia, 46026, Spain
Completed
Madrid, 28009, Spain
Withdrawn
Madrid, 28046, Spain
Completed
MARSEILLE, 13005, France
Withdrawn
PARIS, 75012, France

Primary Outcome

  • Safety: Maximum Tolerated Dose
    MTD is defined as the dose level at which none or 1 of 6 participants experiences dose-limiting toxicity (DLT), when at least 2 of 3-6 participants experience a DLT at the next highest dose
    date_rangeTime Frame:
    approximately after 21 months
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    Safety Issue:
    Yes
  • Safety: Recommended Phase II Dose
    In order to establish a RP2D, the MTD cohort will be expanded to have at least 12 evaluable subjects to confirm the RP2D. It is expected that at least 15 subjects evaluable for DLTs will be necessary to establish the RP2D of the combination"
    date_rangeTime Frame:
    approximately after 21 months
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    Safety Issue:
    Yes
  • Number of participants with Adverse Events
    Individual listings of adverse events will be provided. The incidence of treatment-emergent adverse events and drug-related adverse events, respectively, will be summarized by worst NCI-CTCAE v 4.0 grade and by dose level
    date_rangeTime Frame:
    Dose escalation phase:approximately after 21 months; Expansion Phase: approximately after 21 months
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    Safety Issue:
    Yes
  • AUC(0-24)md based on nominal dosing
    Dose escalation phase has been completed
    date_rangeTime Frame:
    Dose escalation phase:Cycle 1 Day 1, Day 15 and Day 21
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    Safety Issue:
    Yes

Secondary Outcome

  • Overall survival
    date_rangeTime Frame:
    Dose escalation phase: approximately 21 months; Expansion phase: approximately 21 months
    enhanced_encryption
    Safety Issue:
    No
  • Time to progression
    date_rangeTime Frame:
    Dose escalation phase: approximately 21 months; Expansion phase: approximately 21 months
    enhanced_encryption
    Safety Issue:
    No
  • Tumor response: tumor assessment by RECIST v. 1.1
    date_rangeTime Frame:
    Dose escalation phase: approximately 21 months; Expansion phase: approximately 21 months
    enhanced_encryption
    Safety Issue:
    No
  • Taste and texture questionnaire of the regorafenib formulations
    Expansion phase Dose escalation phase
    date_rangeTime Frame:
    Dose escalation phase: Cycle 1; Expansion phase:Concomitant: Cycle 1 Day 1;Sequential: Cycle 1 Day 8
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-24)md based on nominal dosing
    Expansion phase
    date_rangeTime Frame:
    Expansion Phase:Cycle 1 Day1, Day 15 and Day 21
  • Cmax(0-24)md based on individual dosing
    Expansion phase
    date_rangeTime Frame:
    Expansion Phase:Cycle 1 Day1, Day 15 and Day 21
  • Cav(0-24)md based on individual dosing
    Expansion phase Dose escalation phase
    date_rangeTime Frame:
    Expansion phase:Cycle 1 Day1, Day 15 and Day 21; Dose escalation phase:Cycle 1 Day1, Day 15 and Day 21
  • t1/2eff,md based on individual dosing
    Expansion phase Dose escalation phase
    date_rangeTime Frame:
    Expansion phase:Cycle 1 Day1, Day 15 and Day 21; Dose escalation phase:Cycle 1 Day1, Day 15 and Day 21
  • AUC(0-24)md based on individual dosing
    Expansion phase
    date_rangeTime Frame:
    Expansion Phase:Cycle 1 Day1, Day 15 and Day 21
  • Clearance of irinotecan and SN-38
    Expansion phase
    date_rangeTime Frame:
    Expansion Phase:Cycle 1 Day1, Day 15 and Day 21

Trial design

A multi-center, open-label, non-randomized, phase I dose escalation study of regorafenib (BAY 73-4506) in pediatric subjects with solid malignant tumors that are recurrent or refractory to standard therapy
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Other
Allocation
Non-randomized
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
3