Know Cancer

forgot password

Randomized Phase III Trial Comparing Nilotinib 800mg to Imatinib 800 mg for the Treatment of Patients With Advanced and/or Metastatic Gastrointestinal Stromal Tumors Refractory to Imatinib 400 mg

Phase 3
18 Years
Not Enrolling
Gastrointestinal Stromal Tumors

Thank you

Trial Information

Randomized Phase III Trial Comparing Nilotinib 800mg to Imatinib 800 mg for the Treatment of Patients With Advanced and/or Metastatic Gastrointestinal Stromal Tumors Refractory to Imatinib 400 mg

This is an international, randomized, open-label, double-arm, phase III trial that will be
conducted in centers in Latin America, Asia, Europe and Canada. The study will be sponsored
by Novartis Pharmaceuticals Corporation. Patient enrollment will be competitive and will
have a duration of up to 30 months. An interim analysis is planned to occur when
approximately 60% of the PFS events occurs. A total of 150 patients per arm will be enrolled
in the study. Eligible patients will have advanced/metastatic, inoperable GIST of any
anatomical location or recurrent GIST while on or post imatinib adjuvant therapy, with
documented disease progression on therapy with imatinib 400 mg q.d.

Inclusion Criteria:

- Provide a written informed consent.

- Male or female patients ≥ 18 years of age.

- Histologically confirmed diagnosis of GIST of any anatomical location, which is
unresectable and/ or metastatic or recurrent.

- Documented disease progression according to RECIST 1.0. Documentation of progression
required by either 2 CT scans or 2 MRI scans within 6 months prior to randomization
(one image will document the lesion and the other will document the progression by
lesion(s) growth or the presence of new lesion(s)). The interval between the 2
images should be no greater than 6 months apart. Scans will be provided to the
selected imaging CRO.

- Documented disease progression must occur while on imatinib 400 mg PO q.d. Imatinib
therapy could be for (1) unresectable GIST; (2) metastatic GIST; or (3) recurrent
GIST while on imatinib adjuvant therapy or recurrent GIST post adjuvant imatinib

- Positive immunohistochemical staining for c-KIT (CD117) or negative staining for KIT,
but with either positive staining for DOG1 or an identified mutation on KIT or PDGFR

- Presence of at least one measurable lesion according to RECIST 1.0, defined as a
lesion that can be accurately measured in at least one dimension (longest diameter)
as ≥ 20 mm with conventional techniques (conventional CT or MRI scan) or as ≥ 10 mm
with spiral CT scan. Lesions in previously irradiated areas can be considered
measurable only if they have demonstrated clear evidence of progression since the

- A performance status of 0, 1 or 2 according to the Eastern Cooperative Oncology Group
(ECOG) scale (Oken et al 1982)(Appendix A).

- Adequate organ function, as indicated by all of the following:

- White blood cell (WBC) count ≥ 3500/mm3;

- Absolute neutrophil count (ANC) ≥1500/mm3;

- Hemoglobin ≥ 9.0 g/dL;

- Platelet count ≥ 100 x 109/L;

- Total bilirubin ≤ 1.5 X ULN (< 3.0 X ULN if related to disease);

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the
ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times
the ULN;

- Serum creatinine ≤ 1.5 times the ULN;

- Serum amylase and lipase ≤1.5 X ULN;

- Alkaline phosphatase ≤2.5 X ULN (≤ 5.0 X ULN if related to disease);

- Serum potassium, phosphorus, magnesium and calcium ≥ LLN [lower limit of normality]
or correctable with supplements prior to first dose of study drug. (Total calcium
corrected for serum albumin)

- Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days prior to registration.

- Fertile patients (female) must agree to use an acceptable method of contraception to
avoid pregnancy for the duration of the study and for 3 months after study

Exclusion Criteria:

- Prior use of imatinib doses higher than 400 mg q.d. or prior use of any other
tyrosine-kinase inhibitor.

- Tumor progression after stopping imatinib 400 mg q.d.

- No investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C)
prior to the Screening Visit (V100) is allowed with the exception of imatinib

- Cytotoxic, or antineoplastic treatments, such as chemotherapy, immunotherapy,
biological response modifiers, or radiotherapy.

- If the only measurable lesion was previously irradiated and has not shown clear
evidence of progression since the radiotherapy, the patient cannot be included.

- Serious uncontrolled concomitant medical or psychiatric illness.

- Impaired cardiac function including any one of the following:

- LVEF < 45% or below the institutional lower limit of the normal range (whichever is
higher) confirmed by ECHO or Muga

- Inability to determine the QT interval on ECG

- Complete left bundle branch block

- Right bundle branch block plus left anterior or posterior hemiblock

- Use of a ventricular-paced pacemaker

- Congenital long QT syndrome or a known family history of long QT syndrome

- History of or presence of clinically significant ventricular or atrial

- Clinically significant resting bradycardia (<50 bpm);

- QTcF >450 msec on screening ECG (using the QTcF formula). If QTc >450 and
electrolytes are not within normal ranges, electrolytes should be corrected and then
the patient re-screened for QTc;

- History or clinical signs of myocardial infarction within 1 year of study entry

- History of unstable angina within 1 year of study entry

- Other clinically significant heart disease (e.g., congestive heart failureor
uncontrolled hypertension).

- Treatment with strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole,
itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and
the treatment cannot be discontinued or switched to a different medication prior to
starting study drug. (Appendix B).

- Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine,
rifampin, rifabutin, rifapentin, phenobarbitol, St John's Wort), and the treatment
cannot be discontinued or switched to a different medication prior to starting study

- Patients using medication that have been documented to prolong QT interval (see
Appendix B for complete list).

- Grade 3 or higher impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of study drug (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome).

- History of acute pancreatitis within one year of study entry or medical history of
chronic pancreatitis.

- Patients with a history of another primary malignancy that is currently clinically
significant or currently requires active intervention.

- Patients with any other clinically significant medical or surgical condition which,
according to investigators' discretion, should preclude participation; (i.e.: severe
renal disease unrelated to tumor, active or chronic liver disease- hepatitis B or C
virus carriers with normal liver function tests, as described above, can be
included). This includes patient with an acquired bleeding disorder unrelated to

- Use of any investigational agent within 28 days prior to enrollment in the study or
foreseen use of an investigational agent during the study.

- History of non-compliance to medical regimens or inability to grant consent.

- Women who are pregnant, breast feeding, or of childbearing potential without a
negative serum pregnancy test at baseline. Male or female patients of childbearing
potential unwilling to use effective barrier contraceptives throughout the trial and
for 3 months following discontinuation of study drug. Post-menopausal women must
have been amenorrheic for at least 12 months to be considered of non-childbearing

- Inability to comply with the study protocol.

- Patients with a history of CNS metastasis. Note: Patients without clinical signs and
symptoms of CNS involvement are not required to have CT/MRI of the brain.

- Major surgery within 4 weeks prior to randomization or those who have not recovered
from prior surgery

Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.

Outcome Time Frame:

every 6 weeks in the first 6 months and every 8 weeks thereafter

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

June 2009

Completion Date:

August 2012

Related Keywords:

  • Gastrointestinal Stromal Tumors
  • GIST
  • Gastrointestinal Stromal Tumors