Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network

Eur J Cancer. 2020 Aug;135:89-97. doi: 10.1016/j.ejca.2020.04.031. Epub 2020 Jun 15.

Abstract

Background: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nab-paclitaxel monotherapy was further investigated in this phase II study.

Patients and methods: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] + partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR + PR + stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics.

Results: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive.

Conclusions: In this phase II study, limited activity was observed; however, the safety of nab-paclitaxel in paediatric patients was confirmed.

Trial registration: NCT01962103 and EudraCT 2013-000144-26.

Keywords: Albumin-bound paclitaxel; Ewing sarcoma; Neuroblastoma; Paediatric; Rhabdomyosarcoma; Solid tumour.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Albumins / administration & dosage*
  • Albumins / adverse effects
  • Albumins / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Europe
  • Female
  • Humans
  • Infant
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics
  • Progression-Free Survival
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / mortality
  • Rhabdomyosarcoma / pathology
  • Sarcoma, Ewing / drug therapy*
  • Sarcoma, Ewing / mortality
  • Sarcoma, Ewing / pathology
  • Time Factors
  • Tissue Distribution
  • Young Adult

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT01962103
  • EudraCT/2013-000144-26