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 Bruchec & 3 others Ruta Slepetis, Nianhang Chen, Gilles Vassal

Research output: Contribution to journalArticle

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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Investigational Therapies
Pediatrics
Ewing's Sarcoma
Neoplasms
Neutropenia
Maximum Tolerated Dose
Rhabdomyosarcoma
Lymphopenia
130-nm albumin-bound paclitaxel
Leukopenia
Dizziness
Peripheral Nervous System Diseases
Neuroblastoma
Sarcoma
Appointments and Schedules
Pharmacokinetics
Breast Neoplasms
Neoplasm Metastasis
Kidney
Lung

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

In: European Journal of Cancer, Vol. 100, 09.2018, p. 27-34.

Research output: Contribution to journalArticle

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 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, vol. 100, pp. 27-34. https://doi.org/10.1016/j.ejca.2018.05.002
Moreno, Lucas ; Casanova, Michela ; Chisholm, Julia C ; Berlanga, Pablo ; Chastagner, Pascal B ; Baruchel, Sylvain ; Amoroso, Loredana ; Gallego Melcón, Soledad ; Gerber, Nicolas U ; Bisogno, Gianni ; Fagioli, Franca ; Geoerger, Birgit ; Glade Bender, Julia L ; Aerts, Isabelle ; Bergeron, Christophe ; Hingorani, Pooja ; Elias, Ileana ; Simcock, Mathew ; Ferrara, Stefano ; Le Bruchec, Yvan ; Slepetis, Ruta ; Chen, Nianhang ; Vassal, Gilles. / 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. In: European Journal of Cancer. 2018 ; Vol. 100. pp. 27-34.
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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.",
author = "Lucas Moreno and Michela Casanova and Chisholm, {Julia C} and Pablo Berlanga and Chastagner, {Pascal B} and Sylvain Baruchel and Loredana Amoroso and {Gallego Melc{\'o}n}, Soledad and Gerber, {Nicolas U} and Gianni Bisogno and Franca Fagioli and Birgit Geoerger and {Glade Bender}, {Julia L} and Isabelle Aerts and Christophe Bergeron and Pooja Hingorani and Ileana Elias and Mathew Simcock and Stefano Ferrara and {Le Bruchec}, Yvan and Ruta Slepetis and Nianhang Chen and Gilles Vassal",
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year = "2018",
month = "9",
doi = "10.1016/j.ejca.2018.05.002",
language = "English",
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TY - JOUR

T1 - Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours

T2 - A collaboration with innovative therapies for children with cancer

AU - Moreno, Lucas

AU - Casanova, Michela

AU - Chisholm, Julia C

AU - Berlanga, Pablo

AU - Chastagner, Pascal B

AU - Baruchel, Sylvain

AU - Amoroso, Loredana

AU - Gallego Melcón, Soledad

AU - Gerber, Nicolas U

AU - Bisogno, Gianni

AU - Fagioli, Franca

AU - Geoerger, Birgit

AU - Glade Bender, Julia L

AU - Aerts, Isabelle

AU - Bergeron, Christophe

AU - Hingorani, Pooja

AU - Elias, Ileana

AU - Simcock, Mathew

AU - Ferrara, Stefano

AU - Le Bruchec, Yvan

AU - Slepetis, Ruta

AU - Chen, Nianhang

AU - Vassal, Gilles

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

U2 - 10.1016/j.ejca.2018.05.002

DO - 10.1016/j.ejca.2018.05.002

M3 - Article

VL - 100

SP - 27

EP - 34

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -