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| Name | Class |
|---|---|
| Sun Yat-sen University | OTHER |
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For patients of GIST (Gastrointestinal Stromal Tumor), Imatinib has been widely used in GIST with KIT or PDGFRA sensitive mutations. From clinical points of view, individual differences often occur between different patients, leading diverse effect in ADR and drug effect. Meanwhile, the drug effect and adverse drug reaction was significantly influenced by the pharmacokinetic factors and pharmacodynamic and other factors. In this research, we try to establish a more sensitive method to detect sensitive mutations in plasma and discover the correlation between somatic and germline mutations, plasma trough concentration and drug effect, the association between ADME-associated SNP, Target/Receptor/Pathway-associated SNP, trough concentration and TKI adverse effect. Furthermore, in vivo and in vitro research is also crucial for rational explanation for these clinical phenomenon.
The plasma concentration of Imatinib were established. The ADME-associated SNPs included are CYP3A4, CYP3A4, CYP1A1, CYP2C9, CYP2C19, ABCB1, ABCG2, ABCC4, SLC22A1, SLCO1B3 and so on. The Target/Receptor/Pathway-associated SNP s included KIT, PDGFRA, PDGFRB, FLT1, FLT3, MAPK1, SHC1, CCL5, CXCL14 and so on. The somatic mutations included are KIT, PDGFRA, BRAF and so on.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sensitive group; non-sensitive group | sensitive patients were defined as patients reached CR or PR after first month administration,SD after first three months administration. non-sensitive patients were defined as patients reached PD after first month administration and first three months administration. |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | Excluding clinical deterioration without evidence of objective progression according to the Response Evaluation Criteria In Solid Tumors (RECIST), or death from any cause. | The time from the date of randomisation (baseline) to the date of objective tumour progression,and expected average of 36 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with objective response and adverse events | Objective responses (complete response plus partial response) and disease control (objective response plus stable disease≥6 weeks) were established according to RECIST.And adverse events was established according to CTCAE. | one month, three month, 12 month |
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Inclusion Criteria:
Exclusion Criteria:
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GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wei Zhuang, Ph.D | Contact | 86-13427526343 | zhuangw@mail2.sysu.edu.cn | |
| Min Huang, Professor | Contact | 86-020-39943027 | Huangmin@mail.sysu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Min Huang, Professor | Institute of Clinical Pharmacology, SunYat-senU | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Clinical Pharmacology, Sun Yat-sen University | Recruiting | Guangzhou | Guangdong | 510000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23746188 | Background | Angelini S, Ravegnini G, Fletcher JA, Maffei F, Hrelia P. Clinical relevance of pharmacogenetics in gastrointestinal stromal tumor treatment in the era of personalized therapy. Pharmacogenomics. 2013 Jun;14(8):941-56. doi: 10.2217/pgs.13.63. | |
| 19451435 | Background | Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009 Jul 1;27(19):3141-7. doi: 10.1200/JCO.2008.20.4818. Epub 2009 May 18. |
| Label | URL |
|---|---|
| Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center | View source |
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| ID | Term |
|---|---|
| D046152 | Gastrointestinal Stromal Tumors |
| ID | Term |
|---|---|
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| 26851399 | Background | Bouchet S, Poulette S, Titier K, Moore N, Lassalle R, Abouelfath A, Italiano A, Chevreau C, Bompas E, Collard O, Duffaud F, Rios M, Cupissol D, Adenis A, Ray-Coquard I, Bouche O, Le Cesne A, Bui B, Blay JY, Molimard M. Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting. Eur J Cancer. 2016 Apr;57:31-8. doi: 10.1016/j.ejca.2015.12.029. Epub 2016 Feb 4. |
| 23623056 | Background | Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumour. Lancet. 2013 Sep 14;382(9896):973-83. doi: 10.1016/S0140-6736(13)60106-3. Epub 2013 Apr 24. |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |