Primary* To evaluate whether the efficacy of nilotinib is superior to the control arm (as measured by progression free survivalSecondary* To compare the response rate, and time to response, duration of response, and time to tumor progression of…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints
* Progression free survival (PFS)
Secondary outcome
Secondary endpoints
* Response, time-to response, and overall survival
* Safety and tolerability
Background summary
Nilotinib is a second generation inhibitor of the Bcr-Abl tyrosine kinase
which, like imatinib. Nilotinib also inhibits the stem cell factor receptor
c-Kit tyrosine kinase, which is often associated with gastrointestinal stromal
tumors (GIST).
In this study, as of 15 August, 2006, 53 patients (48 imatinib-resistant and 5
imatinib-intolerant) were enrolled. 18 patients received nilotinib alone (400
mg bid), 19 patients escalating doses of nilotinib (200 mg qd, 400 mg qd, or
400 mg bid) in combination with imatinib (400 mg bid), and 16 patients
nilotinib 400 mg bid plus imatinib 400 mg for 8 to 337 days (median 113 days).
The median duration of treatment in patients who received nilotinib alone was
186 days (8-337 days).
39 patients had prior failure of second-line therapies in addition to
progression on imatinib. Thirteen of the 18 patients treated with nilotinib
alone had failed other therapies in addition to imatinib, including sunitinib,
AMG-706, RAD-001or dasatinib.
Of the 18 patients who received nilotinib alone one patient achieved a partial
response lasting approximately 6 months and thirteen patients exhibited disease
stabilization. The median duration of response, including stable disease, was
5.3 months. The estimated median progression free survival (PFS) was
approximately 6 months
.
Study objective
Primary
* To evaluate whether the efficacy of nilotinib is superior to the control arm
(as measured by progression free survival
Secondary
* To compare the response rate, and time to response, duration of response, and
time to tumor progression of nilotinib with the control arm
* To compare overall survival of nilotinib with the control arm
* To assess the safety and tolerability of nilotinib as measured by rate and
severity of adverse events.
Study design
Changed in Amendment 1 into:
This is a randomized, open-label, parallel group, two-arm study with an
Extension study. At Day 1 patients will be randomized in a 2:1 ratio to
nilotinib 400 mg bid arm or the control arm. The control arm includes the
following three options:
Best supportive care or best supportive care plus imatinib or sunitinib at last
tolerated dose.
The choice of one of these options will be at the investigator*s discretion and
patients will not be permitted to switch treatment within this arm.
Intervention
Amendment 1
Arm 1:
2 x daily 400 mg nilotinib (AMN107)
Arm 2 (control arm):
The control arm includes the following three options:
Best supportive care OR
Best supportive care plus imatinib OR
Best supportive care plus sunitinib
The choice of one of these options will be at the investigator*s discretion and
patients will not be permitted to switch treatment within this arm.
Study burden and risks
Toxicity of nilotinib, or imatinib or sunitinib depending on the treatment arm.
Radiation exposure of PET and CT-scan and/or an allergic reaction on the
contrast fluid.
When a biopsy is done, bleeding and pain. The risk of taking blood may include
pain, faint and/or bruisin.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
Amendment 1
* Age * 18 years
* Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent
* Radiological confirmation of disease progression during imatinib therapy at a dose at least 400 mg daily and radiological confirmation of disease progression during sunitinib therapy that was started at 50 mg daily dose OR documented intolerance to imatinib or sunitib, is defined as patients who discontinued imatinib or sunitinib due to any * Grade 3 adverse events that cannot be managed by appropriate supportive care or medical intervention or persist after dose reduction In addition any * grade 2 Adverse event that persist * 1 month in spite of dose interruption and optimal supportive care.
* At least one measurable site of disease (RECIST) a Visit 2
* WHO Performance Status of 0, 1 or 2 at Visit 1 and Visit 2
* Patients must have normal organ, electrolytes, and marrow function at Visit 1 and Visit 2
See also Amendment 1 page 17 - section 2.8 for changes
Exclusion criteria
Amendment 1
* Prior treatment with nilotinib or any other tyrosine kinase inhibitors other than imatinib or sunitinib.
* Treatment with any cytotoxic and/or investigational cytotoxic drug * 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1 with the exception of imatinib and sunitinib
* Prior or concomitant malignancies
* Impaired cardiac function at Visit 1 or 2 (LVEF < 45% ), significant impaired conduction of the heart, use of a cardiac pacemaker, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias or clinically significant resting bradycardia (< 50bpm), QTc > 450 msec, right bundle branch block plus left anterio hemiblock, bifascicular block, myocardial infarction within 12 months prior to Visit 1, unstable angina diagnosed or treated during the past 12 months prior to Visit 1, other clinically significant heart disease
* Patients with severe and/or uncontrolled concurrent medical disease that could cause unacceptable safety risks or compromise compliance with the protocol
* Use of therapeutic coumarin derivatives
* Use of any medications that prolong the QT interval and CYP3A4 inhibitors
* Patients who are pregnant or breast feeding
See also Amendment 1 page 17 section 2.9 for detail on changes
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002267-11-NL |
| CCMO | NL14252.058.06 |