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Tytuł:
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Rationale and design of a prospective, multicenter, phase II clinical trial of safety and efficacy evaluation of long course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer (NCRT-PD1-LARC trial).
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Autorzy:
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Yang Z; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Zhang X; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Zhang J; Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Gao J; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Bai Z; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Deng W; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Chen G; Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
An Y; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Liu Y; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Wei Q; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China.
Han J; Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Li A; Department of General Surgery, Beijing Xuanwu Hospital, Capital Medical University, Beijing, China.
Liu G; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Sun Y; Department of Anorectal, Tianjin People's Hospital, Tianjin, China.
Kong D; Department of Colorectal Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Yao H; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China. .
Zhang Z; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & National Clinical Research Center for Digestive Diseases, Beijing, China. .
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Źródło:
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BMC cancer [BMC Cancer] 2022 Apr 27; Vol. 22 (1), pp. 462. Date of Electronic Publication: 2022 Apr 27.
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Typ publikacji:
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Clinical Trial Protocol; Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: London : BioMed Central, [2001-
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MeSH Terms:
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Neoadjuvant Therapy*/adverse effects
Neoplasms, Second Primary*/therapy
Rectal Neoplasms*/pathology
Rectal Neoplasms*/therapy
Antibodies, Monoclonal, Humanized ; Carcinoma, Transitional Cell ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Male ; Multicenter Studies as Topic ; Prospective Studies ; Urinary Bladder Neoplasms
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References:
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Molecular Sequence:
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ClinicalTrials.gov NCT04911517
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Substance Nomenclature:
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0 (Antibodies, Monoclonal, Humanized)
0KVO411B3N (tislelizumab)
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Entry Date(s):
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Date Created: 20220428 Date Completed: 20220429 Latest Revision: 20220716
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Update Code:
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20240104
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PubMed Central ID:
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PMC9044580
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DOI:
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10.1186/s12885-022-09554-9
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PMID:
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35477432
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Background: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain.
Methods: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes.
Discussion: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC.
Trial Registration: Name of the registry: ClinicalTrials.gov.
Trial Registration Number: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www.
Clinicaltrials: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .
(© 2022. The Author(s).)