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.
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Date
2018-09ICR Author
Author
Moreno, L
Casanova, M
Chisholm, JC
Berlanga, P
Chastagner, PB
Baruchel, S
Amoroso, L
Gallego Melcón, S
Gerber, NU
Bisogno, G
Fagioli, F
Geoerger, B
Glade Bender, JL
Aerts, I
Bergeron, C
Hingorani, P
Elias, I
Simcock, M
Ferrara, S
Le Bruchec, Y
Slepetis, R
Chen, N
Vassal, G
Type
Journal Article
Metadata
Show full item recordAbstract
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/m 2 (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/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . 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/m 2 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/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST.Conclusions nab-Paclitaxel 240 mg/m 2 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.
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Subject
Humans
Neoplasms
Paclitaxel
Albumins
Antineoplastic Agents, Phytogenic
Treatment Outcome
Drug Administration Schedule
Maximum Tolerated Dose
Age Factors
Time Factors
Adolescent
Child
Child, Preschool
Canada
United States
Europe
Female
Male
Drug Dosage Calculations
Research team
Sarcoma Clinical Trials in children and young people
Language
eng
Date accepted
2018-05-01
License start date
2018-09
Citation
European journal of cancer (Oxford, England : 1990), 2018, 100 pp. 27 - 34