07060: Nilotinib in Advanced Gastrointestinal Stromal Tumors (GIST)

• Sponsor: Fox Chase Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00782834
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Duration (Months): 15
• Patients Per Site Per Month: 0.9

Study Details

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.

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 Design

• Study Type: Interventional
• 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: Jul 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Oct 1, 2009

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival Rate at 6 Months [6 months]

   Number of participants that demonstrate progression free survival at 6 months

2. Response Rate [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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 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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT00782834
• Other Study ID Numbers: CAMN107DUS05T
• First Posted: Oct 31, 2008
• Last Update Posted: Apr 22, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Fox Chase Cancer Center: GIST; Nilotinib
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors

Study Results

Participant Flow

Recruitment Details	Patients were accrued between 7/03/2008 and 9/24/2009 at Fox Chase Cancer Center outpatient medical oncology clinics.
Pre-assignment Detail	Advanced GIST with measurable disease; previously treated with at least imatinib and sunitinib; a 5-day washout from prior tyrosine kinase inhibitor therapy. Normal cardiac function with LVEF 45% or >, no history of significant heart disease,arrhythmias,congenital long QT sydrome, heart block, MI within 12 mos of visit 1 or unstable angina, CHF

Arm/Group Title	Nilotinib Arm
Arm/Group Description	All patients treated with nilotinib 400 mg BID orally daily; 4 weeks = one cycle
Period Title: Screened Patients
STARTED	15
COMPLETED	14
NOT COMPLETED	1
Period Title: Screened Patients
STARTED	14
COMPLETED	13
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Nilotinib Arm
Arm/Group Description	All patients treated with nilotinib 400 mg BID orally daily; 4 weeks = one cycle
Overall Participants	15
Age (participants) [Number]
<=18 years	0 0%
Between 18 and 65 years	9 60%
>=65 years	4 26.7%
Gender (participants) [Number]
Female	4 26.7%
Male	9 60%
Region of Enrollment (participants) [Number]
United States	13 86.7%
Primary Site of Cancer (Number) [Number]
Stomach	6 40%
Small Bowel	5 33.3%
Colon	1 6.7%
Rectum	1 6.7%
Prior Tyrosine Kinase Inhibitor (TKI) (Number) [Number]
IM and SU	11 73.3%
IM, SU and NA	1 6.7%
IM, SU, RT and CT	1 6.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival Rate at 6 Months
Description	Number of participants that demonstrate progression free survival at 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib Arm
Arm/Group Description	All patients treated with nilotinib 400 mg BID orally daily; 4 weeks = one cycle
Measure Participants	13
Number [Participants]	13 86.7%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib Arm
Arm/Group Description	All patients treated with nilotinib 400 mg BID orally daily; 4 weeks = one cycle
Measure Participants	13
Number [Participants]	5 33.3%

Adverse Events

Arm/Group Title	Nilotinib Arm
Arm/Group Description	All patients treated with nilotinib 400 mg BID orally daily; 4 weeks = one cycle
All Cause Mortality
	Nilotinib Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nilotinib Arm
	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)
Blood and lymphatic system disorders
Severe anemia	1/13 (7.7%)	1
Gastrointestinal disorders
Pain associated with constipation	2/13 (15.4%)	2
Gastric ulcer	1/13 (7.7%)	1
Nausea vomiting weakness followed by death	1/13 (7.7%)	1
Severe abdominal pain	1/13 (7.7%)	1
General disorders
Profound weakness	1/13 (7.7%)	1
Death	2/13 (15.4%)	2
Infections and infestations
Pneumonia	1/13 (7.7%)	1
Psychiatric disorders
Altered mental status dec pulse ox	1/13 (7.7%)	1
Renal and urinary disorders
Acute azotemia	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Nilotinib Arm
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Leukopenia	6/13 (46.2%)	7
Neutropenia	2/13 (15.4%)	3
Anemia	12/13 (92.3%)	23
Cardiac disorders
Edema	3/13 (23.1%)	5
Gastrointestinal disorders
Nausea	5/13 (38.5%)	9
Vomiting	2/13 (15.4%)	2
Anorexia	7/13 (53.8%)	12
Diarrhea	3/13 (23.1%)	7
Constipation	7/13 (53.8%)	10
GI Pain	5/13 (38.5%)	9
General disorders
Fatigue	13/13 (100%)	23
Hoarseness voice changes	4/13 (30.8%)	5
Infections and infestations
Urinary tract infection	1/13 (7.7%)	2
Investigations
Creatinine	4/13 (30.8%)	5
Alk Phos	6/13 (46.2%)	10
SGOT	4/13 (30.8%)	7
Bilirubin	2/13 (15.4%)	3
Lipase	2/13 (15.4%)	2
Hypoalbuminemia	6/13 (46.2%)	9
Hyponatremia	4/13 (30.8%)	6
Hyperkalemia	5/13 (38.5%)	8
Hypocalcemia	1/13 (7.7%)	1
Hypomagnesemia	4/13 (30.8%)	4
Musculoskeletal and connective tissue disorders
Bone pain	1/13 (7.7%)	3
Arthralgia	4/13 (30.8%)	6
Myalgia	4/13 (30.8%)	7
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/13 (38.5%)	11
Cough	2/13 (15.4%)	4
Skin and subcutaneous tissue disorders
Pruritis	1/13 (7.7%)	1
Rash	5/13 (38.5%)	9

Limitations/Caveats

The study failed to meet its accrual goals. Study terminated prior to accruing 17 subjects due to futility of meeting endpoint.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.