A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved..
PURPOSE: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.
PATIENTS AND METHODS: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.
RESULTS: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.
CONCLUSIONS: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles.
CLINICALTRIALS:.
GOV IDENTIFIER: NCT02835924.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:177 |
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| Enthalten in: |
European journal of cancer (Oxford, England : 1990) - 177(2022) vom: 01. Dez., Seite 154-163 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Argilés, Guillem [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.11.2022 Date Revised 05.01.2023 published: Print-Electronic ClinicalTrials.gov: NCT02835924 Citation Status MEDLINE |
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| doi: |
10.1016/j.ejca.2022.09.037 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348496524 |
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| 100 | 1 | |a Argilés, Guillem |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial) |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.11.2022 | ||
| 500 | |a Date Revised 05.01.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02835924 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a PURPOSE: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients | ||
| 520 | |a PATIENTS AND METHODS: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm | ||
| 520 | |a RESULTS: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C | ||
| 520 | |a CONCLUSIONS: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles | ||
| 520 | |a CLINICALTRIALS: | ||
| 520 | |a GOV IDENTIFIER: NCT02835924 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Drug administration schedule | |
| 650 | 4 | |a Metastasis | |
| 650 | 4 | |a Regorafenib | |
| 650 | 7 | |a regorafenib |2 NLM | |
| 650 | 7 | |a 24T2A1DOYB |2 NLM | |
| 650 | 7 | |a Phenylurea Compounds |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 700 | 1 | |a Mulet, Nuria |e verfasserin |4 aut | |
| 700 | 1 | |a Valladares-Ayerbes, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Viéitez, José M |e verfasserin |4 aut | |
| 700 | 1 | |a Grávalos, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a García-Alfonso, Pilar |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Tobeña, María |e verfasserin |4 aut | |
| 700 | 1 | |a García-Paredes, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Benavides, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Cano, María T |e verfasserin |4 aut | |
| 700 | 1 | |a Loupakis, Fotios |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Garrote, Mercedes |e verfasserin |4 aut | |
| 700 | 1 | |a Rivera, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Goldberg, Richard M |e verfasserin |4 aut | |
| 700 | 1 | |a Cremolini, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Bennouna, Jaafar |e verfasserin |4 aut | |
| 700 | 1 | |a Ciardiello, Fortunato |e verfasserin |4 aut | |
| 700 | 1 | |a Tabernero, Josep M |e verfasserin |4 aut | |
| 700 | 1 | |a Aranda, Enrique |e verfasserin |4 aut | |
| 700 | 0 | |a Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI |e verfasserin |4 aut | |
| 700 | 0 | |a The, REARRANGE investigators |e verfasserin |4 aut | |
| 700 | 0 | |a Principal investigator |e verfasserin |4 aut | |
| 700 | 1 | |a Argilés, Guillem |e verfasserin |4 aut | |
| 700 | 1 | |a Tabernero, Josep |e verfasserin |4 aut | |
| 700 | 0 | |a Steering Committee |e verfasserin |4 aut | |
| 700 | 0 | |a Investigators |e verfasserin |4 aut | |
| 700 | 1 | |a Tabernero, Josep |e investigator |4 oth | |
| 700 | 1 | |a Argilés, Guillem |e investigator |4 oth | |
| 700 | 1 | |a Falcone, Alfredo |e investigator |4 oth | |
| 700 | 1 | |a Ciardiello, Fortunato |e investigator |4 oth | |
| 700 | 1 | |a Goldberg, Richard |e investigator |4 oth | |
| 700 | 1 | |a Bennouna, Jaafar |e investigator |4 oth | |
| 700 | 1 | |a Argilés |e investigator |4 oth | |
| 700 | 1 | |a Tabernero, J |e investigator |4 oth | |
| 700 | 1 | |a Mulet, N |e investigator |4 oth | |
| 700 | 1 | |a Limón, M L |e investigator |4 oth | |
| 700 | 1 | |a Valladares, M |e investigator |4 oth | |
| 700 | 1 | |a Jiménez, P |e investigator |4 oth | |
| 700 | 1 | |a Vieitez, J Ma |e investigator |4 oth | |
| 700 | 1 | |a Grávalos, C |e investigator |4 oth | |
| 700 | 1 | |a García-Alfonso, P |e investigator |4 oth | |
| 700 | 1 | |a Santos, C |e investigator |4 oth | |
| 700 | 1 | |a Páez, D |e investigator |4 oth | |
| 700 | 1 | |a Tobeña, M |e investigator |4 oth | |
| 700 | 1 | |a Sastre, J |e investigator |4 oth | |
| 700 | 1 | |a García Paredes, B |e investigator |4 oth | |
| 700 | 1 | |a Benavides, M |e investigator |4 oth | |
| 700 | 1 | |a Aranda, E |e investigator |4 oth | |
| 700 | 1 | |a Cano, M T |e investigator |4 oth | |
| 700 | 1 | |a Loupakis, F |e investigator |4 oth | |
| 700 | 1 | |a Rguez Garrote, M |e investigator |4 oth | |
| 700 | 1 | |a Guillén, C |e investigator |4 oth | |
| 700 | 1 | |a Rivera, Ma F |e investigator |4 oth | |
| 700 | 1 | |a Safont, J |e investigator |4 oth | |
| 700 | 1 | |a Hiret, S |e investigator |4 oth | |
| 700 | 1 | |a Bennouna, J |e investigator |4 oth | |
| 700 | 1 | |a Pannier, D |e investigator |4 oth | |
| 700 | 1 | |a Malka, D |e investigator |4 oth | |
| 700 | 1 | |a Falcone, A |e investigator |4 oth | |
| 700 | 1 | |a Cremolini, C |e investigator |4 oth | |
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