Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST) (07060)
Primary Purpose
Gastrointestinal Stromal Tumors
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nilotinib
Sponsored by
About this trial
This is an interventional treatment trial for Gastrointestinal Stromal Tumors focused on measuring GIST, Nilotinib
Eligibility Criteria
Inclusion Criteria
- Patients must have histologically or cytologically confirmed GIST
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 millimeters (mm) with conventional techniques or as >= 10 mm with spiral CT scan.
- Patients may have received prior chemotherapy or radiation therapy. Patients must have recovered from any prior therapy and at least 4 weeks (6 weeks for nitrosoureas or mitomycin C; 2 weeks for limited field palliative radiation) must have elapsed since prior treatment.
- Patients must have received and progressed on imatinib and sunitinib. Except for nilotinib, patients may have received additional tyrosine kinase inhibitors or additional targeted therapies.
- Age >= 18 years.
- Life expectancy of greater than 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count >= 1,500/mcL
- platelets >= 100,000/mcL
- total bilirubin <= 1.5 times Upper Limits of Normal (ULN)
- AST(SGOT)/ALT(SGPT) <= 2.5 X ULN OR <= 5.0 X ULN if considered due to tumor
- Potassium, magnesium normal or corrected to normal limits prior to initiating drug
- Calcium, phosphorus normal or corrected to normal limits prior to initiating drug
- creatinine within normal institutional limits
- creatinine clearance 24 hour creatinine clearance >= 50 mL/min (calculation by cockroft formula is acceptable)
- The effects of Nilotinib on the developing human fetus at the recommended therapeutic dose are unknown. Men or women of childbearing potential (WOCBP), to include female partners of heterosexual or bisexual patients, must agree to use an effective method of contraception during the study and for up to three months following termination of the study. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- Patients may not be receiving any other investigational agents within 4 weeks.
- Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ
Impaired cardiac function at baseline, including any one of the following:
- Left Ventricular Ejection Fraction (LVEF)< 45% or below the institutional Lower Limits of Normal (LLN) range (whichever is higher)
- Complete left bundle branch block
- Use of a ventricular paced cardiac pacemaker
- Congenital long QT syndrome or family history of long QT syndrome
- History of or presence of significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (< 50 beats per minute)
- QTc > 450 msec on screening ECG (using the QTcF formula). If QTc > 450 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc.
- Right bundle branch block plus left anterior hemiblock, bifascicular block
- Myocardial infarction within 12 months prior to Visit 1
- Other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
- Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes
- Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon)
- Use of any medications that prolong the QT interval and CYP3A4 inhibitors if the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration. Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval as well as
- Patients who have undergone major surgery <= 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery
- A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits, patients who are pregnant or breast feeding, and patients unwilling or unable to comply with the requirements for the protocol.
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
Sites / Locations
- Fox Chase Cancer Center
Outcomes
Primary Outcome Measures
Progression Free Survival Rate at 6 Months
Number of participants that demonstrate progression free survival at 6 months
Response Rate
Response rate of nilotinib by RECIST criteria evaluated every 2 months for the first 6 months then every 3 months for the duration of treatment period.
Secondary Outcome Measures
Full Information
NCT ID
NCT00782834
First Posted
October 29, 2008
Last Updated
April 15, 2013
Sponsor
Fox Chase Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT00782834
Brief Title
Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST)
Acronym
07060
Official Title
Evaluation of Nilotinib in Advanced GIST Previously Treated With Imatinib and Sunitinib
Study Type
Interventional
2. Study Status
Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
Stopped early for futility, unable to meet accrual goals
Study Start Date
July 2008 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase II study of Nilotinib for patients with advanced GIST that cannot be surgically removed. Patients are candidates for the study if their tumors have progressed on imatinib and sunitinib or if they were intolerant to these drugs. Patients may have received other investigational therapies as well. We are testing the benefit of nilotinib in advanced GIST looking at the length of time disease is controlled as well as the response of the disease to the drug.
Detailed Description
Nilotinib is an oral drug. The dose is 400 mg twice daily
Patients are evaluated every 8 weeks for disease response. Blood work is assessed for safety initially weekly, then every 4 weeks. Physical exams are performed initially weekly and then decreased to every 4 weeks after the first month.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumors
Keywords
GIST, Nilotinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Other Intervention Name(s)
Tasigna
Intervention Description
400 mg orally twice daily until disease progression, intolerability or withdrawal of consent
Primary Outcome Measure Information:
Title
Progression Free Survival Rate at 6 Months
Description
Number of participants that demonstrate progression free survival at 6 months
Time Frame
6 months
Title
Response Rate
Description
Response rate of nilotinib by RECIST criteria evaluated every 2 months for the first 6 months then every 3 months for the duration of treatment period.
Time Frame
1year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients must have histologically or cytologically confirmed GIST
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 millimeters (mm) with conventional techniques or as >= 10 mm with spiral CT scan.
Patients may have received prior chemotherapy or radiation therapy. Patients must have recovered from any prior therapy and at least 4 weeks (6 weeks for nitrosoureas or mitomycin C; 2 weeks for limited field palliative radiation) must have elapsed since prior treatment.
Patients must have received and progressed on imatinib and sunitinib. Except for nilotinib, patients may have received additional tyrosine kinase inhibitors or additional targeted therapies.
Age >= 18 years.
Life expectancy of greater than 12 weeks.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patients must have normal organ and marrow function as defined below:
absolute neutrophil count >= 1,500/mcL
platelets >= 100,000/mcL
total bilirubin <= 1.5 times Upper Limits of Normal (ULN)
AST(SGOT)/ALT(SGPT) <= 2.5 X ULN OR <= 5.0 X ULN if considered due to tumor
Potassium, magnesium normal or corrected to normal limits prior to initiating drug
Calcium, phosphorus normal or corrected to normal limits prior to initiating drug
creatinine within normal institutional limits
creatinine clearance 24 hour creatinine clearance >= 50 mL/min (calculation by cockroft formula is acceptable)
The effects of Nilotinib on the developing human fetus at the recommended therapeutic dose are unknown. Men or women of childbearing potential (WOCBP), to include female partners of heterosexual or bisexual patients, must agree to use an effective method of contraception during the study and for up to three months following termination of the study. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
Patients may not be receiving any other investigational agents within 4 weeks.
Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ
Impaired cardiac function at baseline, including any one of the following:
Left Ventricular Ejection Fraction (LVEF)< 45% or below the institutional Lower Limits of Normal (LLN) range (whichever is higher)
Complete left bundle branch block
Use of a ventricular paced cardiac pacemaker
Congenital long QT syndrome or family history of long QT syndrome
History of or presence of significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia (< 50 beats per minute)
QTc > 450 msec on screening ECG (using the QTcF formula). If QTc > 450 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc.
Right bundle branch block plus left anterior hemiblock, bifascicular block
Myocardial infarction within 12 months prior to Visit 1
Other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes
Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon)
Use of any medications that prolong the QT interval and CYP3A4 inhibitors if the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration. Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval as well as
Patients who have undergone major surgery <= 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery
A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits, patients who are pregnant or breast feeding, and patients unwilling or unable to comply with the requirements for the protocol.
Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret von Mehren, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
12. IPD Sharing Statement
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Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST)
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