Phase 1 study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors
Casanova, M. Bautista, F. Campbell-Hewson, Q. Makin, Guy W J Marshall, L. V. Verschuur, A. Nieto, A. C. Corradini, N. Ploeger, B. Mueller, U.
Casanova, M.
Bautista, F.
Campbell-Hewson, Q.
Makin, Guy W J
Marshall, L. V.
Verschuur, A.
Nieto, A. C.
Corradini, N.
Ploeger, B.
Mueller, U.
Citations
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Abstract
Background and Aims: This phase 1 study evaluated regorafenib plus
vincristine/irinotecan in pediatric patients with rhabdomyosarcoma
(RMS) and other solid tumors.
Methods: Patients with relapsed/refractory tumors received intra-
venous vincristine (1.5 mg/m 2 , Days 1,8) and irinotecan (50 mg/m
2 /day, Days1–5) plus once-daily oral regorafenib (6–<24 months: 60 mg/m
2 escalating to 65 mg/m 2 ;2–<18 years: 72 mg/m 2 escalating to 82
mg/m 2) on either Days 1–14 (concomitant dosing) or Days 8–21 (sequential dosing) during each 21-day cycle. Per protocol, 50% of
patients had to have RMS.
Results: Of 21 treated patients (RMS, n=12; Ewing sarcoma, n=5;
neuroblastoma, n=3; Wilms tumor, n=1), 2 received concomitant (72
mg/m 2 ) and 19 sequential (72 mg/m 2
,n=6; 82 mg/m 2 ,n=13) dos-ing. Median age was 10 years (1.5–17.0). Median number of cycles
was 3 (1–17); irinotecan dose reductions occurred in 62%. Grade
3 dose-limiting toxicities were reported with concomitant (periph-
eral neuropathy and liver injury [1]; pain, vomiting, febrile aplasia
[1]) and sequential (rash and elevated aspartate aminotransferase [1];
thrombocytopenia [1]) dosing. Concomitant dosing was discontinued
Maximum tolerated dose and recommended phase 2 dose (RP2D)
of regorafenib in sequential combination was 82 mg/m 2
. Most com-mon grade 3 toxicities were neutropenia (71%), thrombocytope-
nia (33%), leukopenia (29%), anemia (24%), and alanine aminotrans-ferase increased (24%). Response rate was 38%, including 1 complete
(RMS) and 7 partial responses (5 RMS, 2 Ewing sarcoma); 3 had prior irinotecan. Of 12 patients with RMS, 6 (4 with alveolar subtype) had a
response. Nine patients (43%) had stable disease (maximum 17 cycles).
After the cut-off, 2 additional patients (1 RMS, 1 Ewing sarcoma) had a
partial response.
Conclusions: Regorafenib can be combined at its single-agent RP2D
of 82 mg/m 2 with standard-dose vincristine/irinotecan (with appropri-
ate dose modifications) in pediatric patients with refractory/relapsed
solid tumors in a sequential dosing schedule. Activity was observed in
patients with sarcoma
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Casanova M, Bautista F, Campbell-Hewson Q, Makin GWJ, Marshall LV, Verschuur A, et al. Phase 1 study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors. Pediatric Blood & Cancer. 2020;67:S20-S