Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST)

Gastrointestinal Stromal Tumors Clinical Trial

— 07060  

Official title:

Evaluation of Nilotinib in Advanced GIST Previously Treated With Imatinib and Sunitinib

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00782834
• Other study ID #: CAMN107DUS05T
• Status: Terminated
• Phase: Phase 2
• First received: October 29, 2008
• Last updated: April 15, 2013
• Start date: July 2008
• Est. completion date: October 2009

Study information

• Verified date: April 2013
• Source: Fox Chase Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: October 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Nilotinib
400 mg orally twice daily until disease progression, intolerability or withdrawal of consent

Locations

Country	Name	City	State
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Fox Chase Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival Rate at 6 Months	Number of participants that demonstrate progression free survival at 6 months	6 months	No
Primary	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.	1year	No