Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy

NCT02461849 | Unknown Phase 2

• 1 other identifier: 2013-12-074
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced, Refractory Cancer

Outcome Measures

Primary Outcomes (1)

• Response rate

  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

Secondary Outcomes (4)

• Duration of response

  expected average of 24 weeks

• Progression-free survival

  expected average of 24 weeks

• Overall survival

  expected average of 3years

• Number of subjects with Adverse Events as a measure of safety

  expected average of 24 weeks

Study Arms (1)

Imatinib

EXPERIMENTAL

Imatinib 400mg qd daily Until disease progression, patient's refusal

Drug: Imatinib

Interventions

Imatinib DRUG

Imatinib 400mg qd daily

Imatinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 3, 2015
• Study Start: April 4, 2014
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: June 15, 2022

Record last verified: 2022-06

Locations

KR (1)