A Phase I Dose Finding Study in Children With Solid Tumors Recurrent or Refractory to Standard Therapy

Sponsor
Bayer
Study ID
NCT02085148
Phase
PHASE1
Status
Completed

Conditions

  • Pediatric Oncology

Eligibility Criteria

Sex
ALL
Age
6 Months - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • Regorafenib (BAY73-4506) — DRUG
    Regorafenib will be given orally once a day, across cycles of 21 days each. During each cycle regorafenib is taken for 2 weeks followed by one week off the drug. Doses of the study drug used in this study are age-dependent and the children's dose will been adjusted based on the age and the body surface area and given either as tablets or granulate.
  • Vincristine (Cellcristin®) — DRUG
    Vincristine will be given at a dose of 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg, maximum 2.0 mg) on Day 1 and Day 8 in 21-day cycles.
  • Irinotecan (Irinotecan Cell pharm®) — DRUG
    Irinotecan will be administered at a starting dose of 50 mg/m2/day from Day 1 to Day 5, in 21 day cycles.

Study Details

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 Dates

Start date
Apr 11, 2014
Status verified
Apr 2024
Primary completion
May 5, 2019
Completion
Mar 13, 2024

Study Design

Enrollment
62 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • Experimental: Sequential dosing schedule
    Expansion phase: Schedule B - Sequential dosing schedule: Of a 21-day cycle, regorafenib will be dosed sequentially, following administration of VI: Vincristine：intravenous bolus, 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg), Day 1 and Day 8. Irinotecan: intravenously over 1 hour, 50mg/m2/day, Day 1 to Day 5. Regorafenib: orally, at a starting dose level of 72 mg/m2 (subjects 2 to less than 18 years old) or 60 mg/m2 (subjects 6 to less than 24 months old) once daily, Day 8 to Day 21.
  • Experimental: Concomitant dosing schedule
    Expansion phase: Schedule A - Concomitant dosing schedule: Of a 21-day cycle, regorafenib will be concomitantly administered with vincristine and irinotecan (VI): Vincristine: intravenous bolus, 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg), Day 1 and Day 8. Irinotecan: intravenously over 1 hour, 50 mg/m2/day, Day 1 to Day 5. Regorafenib: orally, at a starting dose level of 72 mg/m2 (subjects 2 to less than 18 years old) or 60 mg/m2 (subjects 6 to less than 24 months old) once daily, Day 1 to Day 14.
  • Experimental: Dose escalation
    Dose escalation phase: This phase of the study has been completed

Primary Outcome Measure

Safety: Maximum Tolerated Dose [ Time Frame: approximately after 21 months ]

Related Studies