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

This study has been terminated.
(Stopped early for futility, unable to meet accrual goals)
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT00782834
First received: October 29, 2008
Last updated: April 15, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Gastrointestinal Stromal Tumors
Drug: Nilotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Nilotinib in Advanced GIST Previously Treated With Imatinib and Sunitinib

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Progression Free Survival Rate at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of participants that demonstrate progression free survival at 6 months

  • Response Rate [ Time Frame: 1year ] [ Designated as safety issue: No ]
    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.


Enrollment: 13
Study Start Date: July 2008
Study Completion Date: October 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Nilotinib
    400 mg orally twice daily until disease progression, intolerability or withdrawal of consent
    Other Name: Tasigna
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00782834

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

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT00782834     History of Changes
Other Study ID Numbers: CAMN107DUS05T
Study First Received: October 29, 2008
Results First Received: December 17, 2010
Last Updated: April 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Fox Chase Cancer Center:
GIST
Nilotinib

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

ClinicalTrials.gov processed this record on November 23, 2014