Clinical trial NCT02461849: Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced, Refractory Cancer
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2015-06-03
Enrollment: 14
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. age ≥ 20
2. advanced, refractory cancer patients who failed standard of care (SOC)
3. 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
4. ECOG performance status of 0\~2
5. measurable or evaluable lesion per RECIST 1.1 criteria
6. 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
7. provision of a signed written informed consent

Exclusion Criteria:

1. severe co-morbid illness and/or active infections
2. pregnant or lactating women
3. history of major surgery or radiotherapy within 4 weeks
4. 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)
5. known history of hypersensitivity to study drugs

Primary outcomes:
measure: Response rate
timeFrame: expected average of 24 weeks
Secondary outcomes:
measure: Duration of response
timeFrame: expected average of 24 weeks
measure: Progression-free survival
timeFrame: expected average of 24 weeks
measure: Overall survival
timeFrame: expected average of 3years
measure: Number of subjects with Adverse Events as a measure of safety
timeFrame: expected average of 24 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: