A Retrospective Pharmacokinetics and Pharmacogenomics Research of Imatinib in Gastrointestinal Stromal Tumor Treatment

NCT03092128 | Unknown DMC

• 1 other identifier: SYSUCC20141021007
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastrointestinal Stromal Tumors; Germline Mutation; Somatic Mutation; Plasma Concentration

Keywords

Gastrointestinal stromal tumor (GIST); Imatinib; Pharmacogenetics; Pharmacokinetics; Precision medicine; Somatic and germ-line mutations

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (1)

• Number of patients with objective response and adverse events

  one month, three month, 12 month

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.

You may qualify if:

• The main patient entry criteria included: age≥ 18 years; histologically and cytologically proved GIST; Eastern cooperative oncology group performance status (ECOGPS)≤2; adequate hematological,renal,and hepatic functions.

Sponsors & Collaborators

• Xueding Wang: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

Institute of Clinical Pharmacology, Sun Yat-sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 23746188 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.

  PMID: 19451435 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.

  PMID: 26851399 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.

  PMID: 23623056 BACKGROUND

Related Links

• Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center

Biospecimen

Retention: SAMPLES WITH DNA

1. FFPE samples of tissue needle biopsy were used for KIT and PDGFRA mutation detection. 2. EDTA-whole blood was centrifuged at 4000rpm\*10min,plasma was separated within four hours for somatic mutation detection.The remaining samples were used for germline mutation detection. All the blood samples were frozen in -80℃ until analysis.

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Min Huang, Professor

  Institute of Clinical Pharmacology, SunYat-senU

  STUDY CHAIR

Central Study Contacts

Wei Zhuang, Ph.D

CONTACT

86-13427526343; zhuangw@mail2.sysu.edu.cn

Min Huang, Professor

CONTACT

86-020-39943027; Huangmin@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Institute of Clinical Pharmacology

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 27, 2017
• Study Start: June 1, 2014
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: September 13, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)