Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST) (07060)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00782834
Recruitment Status : Terminated (Stopped early for futility, unable to meet accrual goals)
First Posted : October 31, 2008
Results First Posted : August 29, 2011
Last Update Posted : April 22, 2013
Information provided by (Responsible Party):
Fox Chase Cancer Center

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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Nilotinib Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Nilotinib in Advanced GIST Previously Treated With Imatinib and Sunitinib
Study Start Date : July 2008
Actual Primary Completion Date : July 2008
Actual Study Completion Date : October 2009

Intervention Details:
    Drug: Nilotinib
    400 mg orally twice daily until disease progression, intolerability or withdrawal of consent
    Other Name: Tasigna

Primary Outcome Measures :
  1. Progression Free Survival Rate at 6 Months [ Time Frame: 6 months ]
    Number of participants that demonstrate progression free survival at 6 months

  2. Response Rate [ Time Frame: 1year ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00782834

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Fox Chase Cancer Center
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center

Additional Information:
Responsible Party: Fox Chase Cancer Center Identifier: NCT00782834     History of Changes
Other Study ID Numbers: CAMN107DUS05T
First Posted: October 31, 2008    Key Record Dates
Results First Posted: August 29, 2011
Last Update Posted: April 22, 2013
Last Verified: April 2013

Keywords provided by Fox Chase Cancer Center:

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases