Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy
A Phase II, Open-label, Study in Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy
KIT is a receptor tyrosine kinase that binds to stem-cell factor (SCF), activating a series of downstream effector pathways. KIT is an established therapeutic target in cancer with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and significant benefit is achieved with various small molecule inhibitors of KIT such as imatinib mesylate. Moreover, there is increasing evidence implicating KIT mutations as tractable therapeutic targets in melanoma. Additional information is required to characterize the functional role of low-frequency mutations in KIT and to determine whether amplification of wild type KIT is a real driver that can be targeted therapeutically. Except GIST and melanoma, other solid cancers were reported to have KIT mutation even in low frequency. A molecular profiling of the tumors of patients referred to the phase I clinic at the M.D. Anderson Cancer Center showed KIT mutation in 7 patients in total of 431 patients (2%).
Hence, the investigators planned this study to apply the molecularly targeted agent, imatinib to various types of cancers harboring KIT mutation or amplification.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
-
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Seoul, Corea, Repubblica di
- Samsung Medical Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- age ≥ 20
- advanced, refractory cancer patients who failed standard of care (SOC)
- KIT aberration: defined as mutation in exons 9, 11, 13, 17 or 18, or nanostring CNV by quantitative PCR (greater than 3 copies) or subject with specific sensitivity (Z-score<-1) to imatinib by Avatar scan whose disease has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy
- ECOG performance status of 0~2
- measurable or evaluable lesion per RECIST 1.1 criteria
adequate marrow, hepatic, renal and cardiac functions
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
- Total serum bilirubin ≤ 1.5 x ULN
- Absolute neutrophil count(ANC) ≥ 1,500/uL
- Platelets ≥ 100,0000/uL
- Hemoglobin ≥ 9.0 g/dL
- provision of a signed written informed consent
Exclusion Criteria:
- severe co-morbid illness and/or active infections
- pregnant or lactating women
- history of major surgery or radiotherapy within 4 weeks
- active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
- known history of hypersensitivity to study drugs
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Imatinib
Imatinib 400mg qd daily Until disease progression, patient's refusal
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Imatinib 400mg qd daily
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Response rate
Lasso di tempo: expected average of 24 weeks
|
Response will be evaluated according to RECIST(Response Evaluation Criteria In Solid Tumors) 1.1 guidelines.Tumor responses will be assessed after the 2cycle chemotherapy and after completion of treatment.
They should be classified as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) according to the Revised Response Criteria for refractory, metastatic cancer harboring KIT mutation or amplification.
|
expected average of 24 weeks
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Durata della risposta
Lasso di tempo: media prevista di 24 settimane
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media prevista di 24 settimane
|
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Progression-free survival
Lasso di tempo: expected average of 24 weeks
|
expected average of 24 weeks
|
|
Overall survival
Lasso di tempo: expected average of 3years
|
expected average of 3years
|
|
Number of subjects with Adverse Events as a measure of safety
Lasso di tempo: expected average of 24 weeks
|
expected average of 24 weeks
|
Collaboratori e investigatori
Sponsor
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Anticipato)
Completamento dello studio (Anticipato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 2013-12-074
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .