TY - JOUR
T1 - Study protocol for SPARED trial
T2 - Randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy
AU - Minatogawa, Hiroko
AU - Izawa, Naoki
AU - Kawaguchi, Takashi
AU - Miyaji, Tempei
AU - Shimomura, Kazuhiro
AU - Kazunori, Honda
AU - Iihara, Hirotoshi
AU - Ohno, Yasushi
AU - Inada, Yusuke
AU - Arioka, Hitoshi
AU - Morita, Hajime
AU - Hida, Naoya
AU - Sugawara, Mitsuhiro
AU - Katada, Chikatoshi
AU - Nawata, Shuichi
AU - Ishida, Hiroo
AU - Tsuboya, Ayako
AU - Tsuda, Takashi
AU - Yamaguchi, Takuhiro
AU - Nakajima, Takako Eguchi
N1 - Funding Information:
Funding This study is supported by Japan Agency for Medical Research and Development (AMED) grant number 19ck0106501h0001. AMED had and will have no involvement in the design and conduct of the study, collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.
Funding Information:
1Department of Pharmacy, St.Marianna University School of Medicine Hospital, Kawasaki, Japan 2Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan 3Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan 4Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 5Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya, Japan 6Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan 7Department of Pharmacy, Gifu University Hospital, Gifu, Japan 8Department of Respirology, Gifu University Graduate School of Medicine, Gifu, Japan 9Department of Pharmacy, Yokohama Rosai Hospital, Yokohama, Japan 10Department of Medical Oncology, Yokohama Rosai Hospital, Yokohama, Japan 11Department of Pharmacy, St. Marianna University Yokohama City Seibu Hospital, Yokohama, Japan 12Department of Internal Medicine, St.Marianna University School of Medicine, Kawasaki, Japan 13Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan 14Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan 15Department of Hospital Pharmaceutics, Showa University Northern Yokohama Hospital, Yokohama, Japan 16Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan 17Department of Pharmacy, St. Marianna University Kawasakishi Municipal Tama Hospital, Kawasaki, Japan 18Department of Hepato-Biliary-Pancreatic Center, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan 19Division of Biostatistics, Tohoku University School of Medicine, Sendai, Japan 20Division of Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, Kyoto, Japan Acknowledgements We are grateful for support from the Japan Agency for Medical Research and Development, Grant-in-Aid for Scientific Research. The authors thank in advance all the patients, investigators and institutions involved in this study.
Publisher Copyright:
©
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Introduction Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens. Methods and analysis This is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m 2 as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1-4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24-120 hours post-CDDP administration). The non-inferiority margin is set at-15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280. Ethics and dissemination The institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals. Trial registration number UMIN000032269.
AB - Introduction Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens. Methods and analysis This is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m 2 as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1-4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24-120 hours post-CDDP administration). The non-inferiority margin is set at-15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280. Ethics and dissemination The institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals. Trial registration number UMIN000032269.
KW - adult palliative care
KW - adverse events
KW - chemotherapy
KW - clinical trials
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U2 - 10.1136/bmjopen-2020-041737
DO - 10.1136/bmjopen-2020-041737
M3 - Article
C2 - 33334838
AN - SCOPUS:85098212570
SN - 2044-6055
VL - 10
JO - BMJ Open
JF - BMJ Open
IS - 12
M1 - e041737
ER -