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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
-
-
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Seoul, Korea, Republikken
- Samsung Medical Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Imatinib
Imatinib 400mg qd daily Until disease progression, patient's refusal
|
Imatinib 400mg qd daily
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Response rate
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Varighed af svar
Tidsramme: forventet gennemsnit på 24 uger
|
forventet gennemsnit på 24 uger
|
|
Progression-free survival
Tidsramme: expected average of 24 weeks
|
expected average of 24 weeks
|
|
Overall survival
Tidsramme: expected average of 3years
|
expected average of 3years
|
|
Number of subjects with Adverse Events as a measure of safety
Tidsramme: expected average of 24 weeks
|
expected average of 24 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 2013-12-074
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