Entacapone Combination With Imatinib for Treatment of GIST
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|ClinicalTrials.gov Identifier: NCT04006769|
Recruitment Status : Active, not recruiting
First Posted : July 5, 2019
Last Update Posted : December 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Gastrointestinal Stromal Tumor, Malignant||Drug: Entacapone Drug: Imatinib Mesylate||Early Phase 1|
Most patients with Metastatic/unresectable Gastrointestinal stromal tumors will progress on the treatment of tyrosine kinase inhibitor(TKI) including Imatinib and Sunitinib.
Entacapone and imatinib can each inhibit the role of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog(KIT) which is a kind of transmembrane receptor tyrosine kinase promoting the clonal proliferation and growth of GIST cells, but they do so by different mechanisms.
Entacapone has been approved from China Food and Drug Administration(cFDA) for controlling the symptom of Parkinson' s disease in the combination with levodopa. Recently, entacapone was identified to be an inhibitor of Fat mass and obesity-associated protein(FTO) enzyme, which was reported as the first N6-methyladenosine (m6A) demethylase of eukaryotic messenger RNA(mRNA). Entacapone can inhibit the transcriptional level of KIT mRNA leading to the decreased expression of KIT protein.
Imatinib mesylate, an oral multiple TKI targeting the KIT-oncoprotein, was the standard first-line therapy of c-KIT-mutated GISTs. Imatinib can prohibit the activation of mutated c-KIT tyrosine kinase and then impede the kinase cascade of c-KIT signal pathway.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Entacapone in Combination With Imatinib Mesylate for Treatment of Patients With Gastrointestinal Stromal Tumors(GIST) Following Failure of at Least Imatinib and Sunitinib|
|Actual Study Start Date :||October 30, 2020|
|Actual Primary Completion Date :||June 13, 2021|
|Estimated Study Completion Date :||January 1, 2025|
Experimental: Entacapone & Imatinib mesylate
Entacapone 200mg tablet (Orion pharma,Switzerland) by mouth, three times a day and then escalated to final dose of 1.0 grams three times per day within one week, until disease progression, intolerable toxicity, or withdrawal of informed consent, whichever occurs first.
And Imatinib mesylate 400mg tablet by mouth, once a day until disease progression, intolerable toxicity, or withdrawal of informed consent, whichever occurs first.
Drug: Imatinib Mesylate
Imatinib Mesylate tablet
Other Name: Gleevec
- Objective response rate(ORR) [ Time Frame: day 30, day 90, day 180. ]The ORR is the proportion of the patients who achieved complete response (CR) or partial responses(PR) according to CHOI criteria or Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
- Disease control rate(DCR) [ Time Frame: day 30, day 90, day 180. ]The ORR is the proportion of the patients who achieved complete response (CR) or partial responses(PR) and stable disease(SD) according to CHOI criteria or Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
- Adverse events（AE) and serious adverse events(SAE) [ Time Frame: day 30, day 60, day 90, day 120, day 150, day 180. ]The ratio of AE and SAE which were defined by the Common Terminology Criteria for Adverse Events,CTCAE)
- Quality of Life(QOL) [ Time Frame: day 30, day 90, day 180. ]The data was collected using EORTC QLQ-C30 V3.0 questionnaire
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04006769
|Bin Li, MD|
|Changsha, Hunan, China, 410008|
|Principal Investigator:||Bin Li, MD||Xiangya Hospital, Central South University, Changsha, Hunan,China,410008|