Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer

Lucas Moreno, Michela Casanova, Julia C Chisholm, Pablo Berlanga, Pascal B Chastagner, Sylvain Baruchel, Loredana Amoroso, Soledad Gallego Melcón, Nicolas U Gerber, Gianni Bisogno, Franca Fagioli, Birgit Geoerger, Julia L Glade Bender, Isabelle Aerts, Christophe Bergeron, Pooja Hingorani, Ileana Elias, Mathew Simcock, Stefano Ferrara, Yvan Le BruchecRuta Slepetis, Nianhang Chen, Gilles Vassal

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Abstract

BACKGROUND: nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported.

PATIENTS AND METHODS: Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D).

RESULTS: Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m2 and grade 4 neutropenia >7 days at 270 mg/m2. The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1-2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m2. Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST.

CONCLUSIONS: nab-Paclitaxel 240 mg/m2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. CLINICALTRIALS.GOV: NCT01962103.

EUDRACT: 2013-000144-26.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalEuropean Journal of Cancer
Volume100
DOIs
Publication statusPublished - Sep 2018

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Moreno, L., Casanova, M., Chisholm, J. C., Berlanga, P., Chastagner, P. B., Baruchel, S., Amoroso, L., Gallego Melcón, S., Gerber, N. U., Bisogno, G., Fagioli, F., Geoerger, B., Glade Bender, J. L., Aerts, I., Bergeron, C., Hingorani, P., Elias, I., Simcock, M., Ferrara, S., ... Vassal, G. (2018). Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. European Journal of Cancer, 100, 27-34. https://doi.org/10.1016/j.ejca.2018.05.002