A Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs

NCT02712112 | Completed Phase 2

• 1 other identifier: AMC1601
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Recent preclinical study has suggested a potential possibility that imatinib might promote tumor growth in the presence of secondary resistance mutations \[10\]. This result imply that intermittent dosing schedule of imatinib rechallenge might be better than continuous dosing schedule in terms of controlling tumors harboring secondary resistance mutations. In addition, in these heavily pretreated patients, even mild grade of toxicity may significantly impair quality of life, and intermittent dosing schedule may have an advantage in this context. Therefore, investigators hypothesize that intermittent dosing schedule of imatinib rechallenge might be feasible and effective in patients with TKI-refractory GISTs. This study will assess the feasibility of intermittent imatinib dosing schedule in patients with GISTs who had failures from both imatinib and sunitinib.

Conditions

Gastrointestinal Stromal Tumors (GISTs)

Outcome Measures

Primary Outcomes (1)

• disease control rate

  disease control rate at 12 weeks

  at 12 weeks

Study Arms (2)

Intermittent dosing arm

EXPERIMENTAL

one-week on and one-week off schedule(Imatinib Mesylate, 400 mg once daily, oral)

Drug: Imatinib Mesylate

Continuous dosing arm

SHAM COMPARATOR

continuous dosing without off-treatment schedule(Imatinib Mesylate, 400 mg once daily, oral)

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

Continuous dosing arm; Intermittent dosing arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 19 years and older
• Patients with metastatic or unresectable GIST which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
• Prior clinical benefit from 1st line imatinib defined as CR, PR, or SD at 6 months after the start of 1st line imatinib
• Patients whose disease has progressed with at least both prior imatinib (400mg/day) and sunitinib therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 \~ 3
• Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
• Adequate renal function, with serum creatinine \< 1.5 x upper limit of normal (ULN)
• Adequate hepatic function with serum total bilirubin \< 1.5 x ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5 x ULN in the absence of liver metastases, or \< 5 x UNL in the presence of liver metastases.
• Expected life expectancy of greater than 12 weeks in the absence of any intervention
• No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent \> 5 years previously without evidence of relapse
• Written informed consent to the study

You may not qualify if:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
• Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
• Obstruction of gastrointestinal tract
• Active gastrointestinal bleeding
• Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
• Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

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 Officials

• Min-Hee Ryu, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 18, 2016
• Study Start: March 16, 2016
• Primary Completion: June 15, 2019
• Study Completion: June 15, 2019
• Last Updated: January 4, 2023

Record last verified: 2022-12

Locations

KR (1)