Clinical trial NCT00782834: Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST)
Official title: Evaluation of Nilotinib in Advanced GIST Previously Treated With Imatinib and Sunitinib
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: GIST
Nilotinib
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
First posted: 2008-10-31
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival Rate at 6 Months
timeFrame: 6 months
measure: Response Rate
timeFrame: 1year
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Margaret von Mehren, MD
role: PRINCIPAL_INVESTIGATOR
References: