Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer
4. marts 2022 opdateret af: Fujian Cancer Hospital
TACTIC: a Phase II Study of TAS-102 Monotherapy and Thalidomide Plus TAS-102 as Third-line Therapy and Beyond in Patients With Advanced Colorectal Carcinoma
Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.
Studieoversigt
Status
Rekruttering
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
In the past decade, the use of targeted drugs has greatly improved the overall survival of patients with mCRC. However, there are currently few effective drugs available clinically. Trifluridine/Tipiracil (TAS-102) is a novel cytotoxic antitumor drug taken orally with minor adverse reactions, consisting of trifluridine and tipyrimidine hydrochloride. Tas-102 has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if RAS wild type, an anti-EGFR therapy. Multiple studies have shown that TAS-102 prolongs median OS and PFS in mCRC patients compared with placebo.
Thalidomide is a sedative that was developed in the late 1950s and eventually marketed and prescribed in several countries to pregnant women to alleviate nausea in the late 1950s and early 1960s. The drug, however, caused severe birth defects in more than 10,000 children worldwide and was forced to withdraw from the international market. Further studies found that the S-optical isomer of thalidomide can inhibit neutrophil chemotaxis, produce anti-inflammatory activity, stimulate immune system activation, regulate immunity, anti-angiogenesis, and inhibit the adhesion of cancer cells to stroma, so as to change the microenvironment of the body, and achieve anti-tumor effect.
Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.
Undersøgelsestype
Interventionel
Tilmelding (Forventet)
120
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Zengqing Guo
- Telefonnummer: +86 13860603879
- E-mail: gzq_005@126.com
Studiesteder
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Fuzhou, Kina
- Ikke rekrutterer endnu
- First Affiliated Hospital of Fujian Medical University
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Kontakt:
- Rixiong Rixiong Wang
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Fuzhou, Kina
- Ikke rekrutterer endnu
- Fujian Provincial People's Hospital
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Kontakt:
- Wujin Chen
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Fuzhou, Kina
- Ikke rekrutterer endnu
- Fuzhou First Hospital affiliated to Fujian Medical University
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Kontakt:
- Jingrong Liu
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Fuzhou, Kina
- Ikke rekrutterer endnu
- Hospital 900 of the Joint Logistic Support Force of the Chinese People's Liberation Army
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Kontakt:
- Fangwei Xie
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Fuzhou, Kina
- Ikke rekrutterer endnu
- The Third People's Hospital affiliated to Fujian University of Chinese Medicine
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Kontakt:
- Wenwu Wang
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Fujian
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Fuzhou, Fujian, Kina
- Rekruttering
- Fujian Medical University Cancer Hospital, Fujian Cancer Hospital
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Kontakt:
- Zengqing Zengqing Guo
- Telefonnummer: +86 13860603879
- E-mail: gzq_005@126.com
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-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 75 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
- Have histological or cytological documentation of adenocarcinoma of the colon or rectum (mCRC).
- For patients with disease progression after conventional treatment, TAS-102 is determined as the third-line therapy or beyond according to the routine treatment practice of the researcher.
- Aged no less than 20 years.
5.Have a measurable disease, according to RECIST version 1.1 6.Eastern Cooperative Oncology Group performance status 0-2. 7.Life expectancy of at least 12 weeks. 8.For women with reproductive potential, serum tests were performed within 7 days before the start of study treatment β- Human chorionic gonadotropin (β- HCG) pregnancy test, the result is negative. Women with reproductive potential must agree to take appropriate contraceptive measures with informed consent until at least 6 months after the last use of the study drug.
9.Sufficient bone marrow, liver and kidney functions and meet the following laboratory requirements:
- Platelet count ≥75 × 109 /L
- Hemoglobin level ≥90 g/L
- Absolute neutrophil count ≥1.5× 109 /L
a) Total bilirubin ≤1.5 × upper limit of normal (ULN) b) Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) d) Serum creatinine ≤1.5 × ULN e) Glomerular filtration rate ≥30 ml/min/1.73 m2, according to the modified diet in renal disease abbreviated formula 10.Able to take oral drugs. 11.Have signed written informed consent.
Exclusion criteria
- With arterial or venous thrombosis or embolic events such as myocardial infarction, cerebral thrombosis, intracerebral hemorrhage, deep venous thrombosis or pulmonary embolism within 6 months before the start of the study.
- Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (adverse events per CTCAE v5.0) within 4 weeks prior to the start of treatment.
- Peripheral neuropathy > grade 1 (adverse events per CTCAE v5.0).
- History of uncontrolled or medicated heart disease.
- Seizure disorder requiring medication.
- Known history of human immunodeficiency virus (HIV) infection.
- Patients with an active infection.
- Other uncontrolled concurrent diseases determined by the researchers as not meeting the study conditions.
- Patients with ascites and pleural effusion with clinical symptoms requiring treatment.
- Known allergy to any of the study drug ingredients.
- Unable to swallow oral medication.
- Prior exposure to TAS-102 or thalidomide.
- Patients who have brain metastases.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: TAS-102+Thalidomide
Thalidomide 100mg PO BID+TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
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For the experimental group, the intervention was thalidomide（100mg PO Bid)
Andre navne:
TAS-102
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Aktiv komparator: TAS-102
TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
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TAS-102
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Progressionsfri overlevelse (PFS)
Tidsramme: Fra randomiseringsdatoen til datoen for første dokumenterede progression eller dødsdato uanset årsag, alt efter hvad der kom først, vurderet op til 100 måneder
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PFS blev defineret som tiden fra randomisering til datoen for første forekomst af investigator-vurderet radiologisk sygdomsprogression eller død på grund af en hvilken som helst årsag, alt efter hvad der kom først.
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Fra randomiseringsdatoen til datoen for første dokumenterede progression eller dødsdato uanset årsag, alt efter hvad der kom først, vurderet op til 100 måneder
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Samlet overlevelse (OS)
Tidsramme: Fra randomiseringsdatoen til datoen for dødsfald uanset årsag, alt efter hvad der kom først, vurderet op til 100 måneder
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OS blev defineret som tiden fra datoen for randomisering til datoen for dødsfald på grund af en hvilken som helst årsag.
For forsøgspersoner, der var i live eller mistet til opfølgning på dataanalysens skæringsdato, blev overlevelse censureret på forsøgspersonens sidst kendte overlevelsestidspunkt.
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Fra randomiseringsdatoen til datoen for dødsfald uanset årsag, alt efter hvad der kom først, vurderet op til 100 måneder
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Forekomst af behandlings-opståede bivirkninger
Tidsramme: fra første dosis til inden for 30 dage efter den sidste dosis
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Hyppigheden af behandlings-opståede bivirkninger blev evalueret i overensstemmelse med NCI CTC AE Version 5.0
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fra første dosis til inden for 30 dage efter den sidste dosis
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313.
- Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9.
- Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.
- Ma J, Yang QL, Ling Y. Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer. BMC Cancer. 2017 Feb 14;17(1):132. doi: 10.1186/s12885-017-3133-8.
- Andersen SE, Andersen IB, Jensen BV, Pfeiffer P, Ota T, Larsen JS. A systematic review of observational studies of trifluridine/tipiracil (TAS-102) for metastatic colorectal cancer. Acta Oncol. 2019 Aug;58(8):1149-1157. doi: 10.1080/0284186X.2019.1605192. Epub 2019 Apr 19.
- Wallander M, Rolander B, Avall-Lundqvist E, Elander NO. Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer. J Gastrointest Oncol. 2020 Aug;11(4):616-625. doi: 10.21037/jgo-20-43.
- Longo-Munoz F, Argiles G, Tabernero J, Cervantes A, Gravalos C, Pericay C, Gil-Calle S, Mizuguchi H, Carrato-Mena A, Limon ML, Garcia-Carbonero R. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial. Clin Transl Oncol. 2017 Feb;19(2):227-235. doi: 10.1007/s12094-016-1528-7. Epub 2016 Jul 21.
- Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. doi: 10.1056/NEJMoa1414325.
- Yoshida Y, Yamada T, Matsuoka H, Sonoda H, Fukazawa A, Yoshida H, Ishida H, Hirata K, Hasegawa S, Sakamoto K, Otsuka T, Koda K. A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study). J Anus Rectum Colon. 2019 Jul 30;3(3):136-141. doi: 10.23922/jarc.2018-043. eCollection 2019.
- Liu H, Ma Y, Xu HC, Huang LY, Zhai LY, Zhang XR. Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept. Curr Eye Res. 2020 Dec;45(12):1467-1476. doi: 10.1080/02713683.2020.1781193. Epub 2020 Jul 7.
- Kotani D, Kuboki Y, Horasawa S, Kaneko A, Nakamura Y, Kawazoe A, Bando H, Taniguchi H, Shitara K, Kojima T, Tsuji A, Yoshino T. Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer. BMC Cancer. 2019 Dec 27;19(1):1253. doi: 10.1186/s12885-019-6475-6.
- Eriksson T, Bjorkman S, Roth B, Fyge A, Hoglund P. Enantiomers of thalidomide: blood distribution and the influence of serum albumin on chiral inversion and hydrolysis. Chirality. 1998;10(3):223-8. doi: 10.1002/(SICI)1520-636X(1998)10:33.0.CO;2-A.
- Zhang L, Qu X, Teng Y, Shi J, Yu P, Sun T, Wang J, Zhu Z, Zhang X, Zhao M, Liu J, Jin B, Luo Y, Teng Z, Dong Y, Wen F, An Y, Yuan C, Chen T, Zhou L, Chen Y, Zhang J, Wang Z, Qu J, Jin F, Zhang J, Jin X, Xie X, Wang J, Man L, Fu L, Liu Y. Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study). J Clin Oncol. 2017 Nov 1;35(31):3558-3565. doi: 10.1200/JCO.2017.72.2538. Epub 2017 Aug 30.
- Melchert M, List A. The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. doi: 10.1016/j.biocel.2007.01.022. Epub 2007 Jan 30.
- Chen C, Yu G, Xiao W, Xing M, Ni J, Wan R, Hu G. Thalidomide inhibits proliferation and epithelial-mesenchymal transition by modulating CD133 expression in pancreatic cancer cells. Oncol Lett. 2017 Dec;14(6):8206-8212. doi: 10.3892/ol.2017.7213. Epub 2017 Oct 18.
- 中国临床肿瘤学会（CSCO）.抗肿瘤治疗相关恶心呕吐预防和治疗指南（M）.（2019.V1.0）
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. oktober 2021
Primær færdiggørelse (Forventet)
31. december 2022
Studieafslutning (Forventet)
1. december 2023
Datoer for studieregistrering
Først indsendt
13. januar 2022
Først indsendt, der opfyldte QC-kriterier
23. februar 2022
Først opslået (Faktiske)
4. marts 2022
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
18. marts 2022
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
4. marts 2022
Sidst verificeret
1. januar 2022
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Neoplasmer
- Neoplasmer efter sted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Tyktarmssygdomme
- Tarmsygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Kolorektale neoplasmer
- Lægemidlers fysiologiske virkninger
- Anti-infektionsmidler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Angiogenese-hæmmere
- Angiogenesemodulerende midler
- Vækststoffer
- Væksthæmmere
- Antibakterielle midler
- Leprostatiske midler
- Thalidomid
Andre undersøgelses-id-numre
- TACTIC
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