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A global phase II randomized trial comparing oral taxane ModraDoc006/r to intravenous docetaxel in metastatic castration resistant prostate cancer

UN. Vaishampayan, M. Keessen, R. Dreicer, EI. Heath, T. Buchler, PF. Árkosy, T. Csöszi, P. Wiechno, E. Kopyltsov, SV. Orlov, A. Plekhanov, M. Smagina, S. Varlamov, ND. Shore

. 2024 ; 202 (-) : 114007. [pub] 20240311

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu randomizované kontrolované studie, klinické zkoušky, fáze II, časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24014108

STUDY AIM: ModraDoc006, an oral formulation of docetaxel, is co-administered with the cytochrome P450-3A4 and P-glycoprotein inhibitor, ritonavir (r): ModraDoc006/r. The preliminary efficacy and safety of oral ModraDoc006/r was evaluated in a global randomized phase II trial and compared to the current standard chemotherapy regimen of intravenous (i.v.) docetaxel and prednisone. METHODS: 103 mCRPC patients, chemotherapy-naïve with/without abiraterone and/or enzalutamide pretreated, with adequate organ function and evaluable disease per RECIST v1.1 and PCWG3 guidelines were randomized 1:1 into two cohorts. In Cohort 1, 49 patients received docetaxel 75 mg/m2 i.v. every 3 weeks (Q3W). In Cohort 2, 52 patients received ModraDoc006/r; 21 patients with a starting dose of ModraDoc006 30 mg with ritonavir 200 mg in the morning and ModraDoc006 20 mg with ritonavir 100 mg in the evening (30-20/200-100 mg) bi-daily-once-weekly (BIDW) on Days 1, 8, and 15 of a 21-day cycle. To alleviate tolerability, the starting dose was amended to ModraDoc006/r 20-20/200-100 mg in another 31 patients. All patients received prednisone 10 mg daily. Primary endpoint was rPFS. RESULTS: There was no significant difference in rPFS between the 2 arms (p = 0.1465). Median rPFS was 9.5 months and 11.1 months (95% CI) for ModraDoc006/r and i.v. docetaxel, respectively. Partial response was noted in 44.1% and 38.7% measurable disease patients, and 50% decline of PSA was seen in 23 (50%) and 26 (56.5%) evaluable cases treated with ModraDoc006/r and i.v. docetaxel, respectively. The safety profile of ModraDoc006/r 20-20/200-100 mg dose was significantly better than i.v. docetaxel, with mild (mostly Grade 1) gastrointestinal toxicities, no hematologic adverse events, and neuropathy and alopecia incidence of 11.5% and 25%, respectively. CONCLUSIONS: ModraDoc006/r potentially represents a widely applicable, convenient, effective, and better tolerated oral taxane therapy option for mCRPC. Further investigation of ModraDoc006/r in a large randomized trial is warranted.

Citace poskytuje Crossref.org

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$a STUDY AIM: ModraDoc006, an oral formulation of docetaxel, is co-administered with the cytochrome P450-3A4 and P-glycoprotein inhibitor, ritonavir (r): ModraDoc006/r. The preliminary efficacy and safety of oral ModraDoc006/r was evaluated in a global randomized phase II trial and compared to the current standard chemotherapy regimen of intravenous (i.v.) docetaxel and prednisone. METHODS: 103 mCRPC patients, chemotherapy-naïve with/without abiraterone and/or enzalutamide pretreated, with adequate organ function and evaluable disease per RECIST v1.1 and PCWG3 guidelines were randomized 1:1 into two cohorts. In Cohort 1, 49 patients received docetaxel 75 mg/m2 i.v. every 3 weeks (Q3W). In Cohort 2, 52 patients received ModraDoc006/r; 21 patients with a starting dose of ModraDoc006 30 mg with ritonavir 200 mg in the morning and ModraDoc006 20 mg with ritonavir 100 mg in the evening (30-20/200-100 mg) bi-daily-once-weekly (BIDW) on Days 1, 8, and 15 of a 21-day cycle. To alleviate tolerability, the starting dose was amended to ModraDoc006/r 20-20/200-100 mg in another 31 patients. All patients received prednisone 10 mg daily. Primary endpoint was rPFS. RESULTS: There was no significant difference in rPFS between the 2 arms (p = 0.1465). Median rPFS was 9.5 months and 11.1 months (95% CI) for ModraDoc006/r and i.v. docetaxel, respectively. Partial response was noted in 44.1% and 38.7% measurable disease patients, and 50% decline of PSA was seen in 23 (50%) and 26 (56.5%) evaluable cases treated with ModraDoc006/r and i.v. docetaxel, respectively. The safety profile of ModraDoc006/r 20-20/200-100 mg dose was significantly better than i.v. docetaxel, with mild (mostly Grade 1) gastrointestinal toxicities, no hematologic adverse events, and neuropathy and alopecia incidence of 11.5% and 25%, respectively. CONCLUSIONS: ModraDoc006/r potentially represents a widely applicable, convenient, effective, and better tolerated oral taxane therapy option for mCRPC. Further investigation of ModraDoc006/r in a large randomized trial is warranted.
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$a Keessen, Marianne $u Modra Pharmaceuticals B.V., Amsterdam, Netherlands. Electronic address: mariannekeessen@gmail.com
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$a Dreicer, Robert $u University of Virginia, Charlottesville, VA, USA
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$a Heath, Elisabeth I $u Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
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$a Buchler, Tomas $u Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic
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$a Árkosy, Péter F $u Debrecen Institute of Oncology, Debrecen, Hungary
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$a Csöszi, Tibor $u Hetenyi G Korhaz, Szolnok, Hungary
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$a Wiechno, Pawel $u Klinika Nowotworów Układu Moczowego Centrum Onkologii, Warsaw, Poland
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$a Kopyltsov, Evgeny $u State Institution of Healthcare, Omsk, Russian Federation
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$a Orlov, Sergey V $u Pavlov First St. Petersburg State Medical University, Saint Petersburg, Russian Federation
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$a Plekhanov, Alexey $u Clinic "Andros" LLC, Saint Petersburg, Russian Federation
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$a Smagina, Maria $u Leningrad Regional Oncology Dispensary, Saint Petersburg, Russian Federation
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$a Varlamov, Sergei $u Altai Regional Cancer Center, Barnaul, Russian Federation
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$a Shore, Neal D $u Carolina Urologic Research Center, Myrtle Beach, SC, USA
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