Gastrointestinal Stromal TumorsNCT03092128
A Retrospective Pharmacokinetics and Pharmacogenomics Research of Imatinib in Gastrointestinal Stromal Tumor Treatment
An observational study of Gastrointestinal Stromal Tumors and Germline Mutation, run by Xueding Wang at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gastrointestinal Stromal Tumors, Germline Mutation, Somatic Mutation
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- Jun 2014to Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.
Who may be able to join
- 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.
Who cannot join
- uncontrolled systemic disease,and other chemotherapy at the time of inclusion. The protocol was approved by the Ethical Committee of Cancer Center of Sun Yat-Sen University (CCSU), and written informed consent was obtained form each patient.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of Clinical Pharmacology, Sun Yat-sen University
Guangzhou, Guangdong, 510000
Wei Zhuang, Ph. D, 86-13427526343, zhuangw@mail2.sysu.edu.cn
Min Huang, Professor, +86 020 87331409 ext. 101, huangmin@mail.sysu.edu.cn
About this study
Official title: Retrospective Study Based on Pharmacokinetics, Somatic Mutations and Genetic Polymorphisms Related to Individual Variations of Drug Effect and Adverse Drug Reaction of Imatinib in Gastrointestinal Stromal Tumor Treatment.
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.
Read the detailed description
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.
- 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
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: one month, three month, 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study startJun 2014
- Primary completionJun 2019 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xueding Wang
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-sen University
- Responsible party
- Sponsor-investigator, Xueding Wang, Sun Yat-sen University
- Investigators
- Min Huang, Professor, Study chair, Institute of Clinical Pharmacology, SunYat-senU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092128
- Sponsor's protocol ID
- SYSUCC20141021007
- Status last verified
- Sep 2018
- First submitted
- 21 Mar 2017
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23746188Demetri 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.
PubMed 19451435Bouchet 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.
PubMed 26851399Joensuu 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.
PubMed 23623056
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Study Based on Pharmacokinetics, Somatic Mutations and Genetic Polymorphisms Related to Individual Variations of Drug Effect and Adverse Drug Reaction of Imatinib in Gastrointestinal Stromal Tumor Treatment.
- ClinicalTrials.gov ID
- NCT03092128
- Acronym / sponsor ID
- SYSUCC20141021007
- 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
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Xueding WangUniversity, hospital or other
- Collaborators
- Sun Yat-sen University
- Study start
- Jun 2014 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 27 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- GIST (Gastrointestinal stromal tumor) patients; administrated with Imatinib and Sunitinib.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- uncontrolled systemic disease,and other chemotherapy at the time of inclusion. The protocol was approved by the Ethical Committee of Cancer Center of Sun Yat-Sen University (CCSU), and written informed consent was obtained form each patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Progression free survival
Time frame: The time from the date of randomisation (baseline) to the date of objective tumour progression，and expected average of 36 months.
Excluding clinical deterioration without evidence of objective progression according to the Response Evaluation Criteria In Solid Tumors (RECIST), or death from any cause.
1 secondary outcome
Number of patients with objective response and adverse events
Time frame: one month, three month, 12 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Background: PubMed 23746188Angelini 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.
- Background: PubMed 19451435Demetri 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.
- Background: PubMed 26851399Bouchet 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.
- Background: PubMed 23623056Joensuu 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.
- Institute of Clinical Pharmacology, Sun Yat-sen UniversityLink provided by the sponsor.
- Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Min Huang, Professor study chair
Institute of Clinical Pharmacology, SunYat-senU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gastrointestinal Stromal Tumors and Germline Mutation, run by Xueding Wang at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wei Zhuang, Ph.D (86-13427526343, zhuangw@mail2.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: The time from the date of randomisation (baseline) to the date of objective tumour progression，and expected average of 36 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03092128, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.