Clinical trial NCT00135005: Study of AMN107 With Imatinib in Gastrointestinal Stromal Tumors (GIST)
Official title: A Phase I Multicenter, Dose Escalation Study of AMN107 in Combination With Imatinib on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant Gastrointestinal Stromal Tumors (GIST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Stromal Tumors
Keywords: GIST
AMN107
Gastrointestinal Stromal Tumors
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-08-25
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an open-label, multicenter, Phase I dose-escalation study of the combination of AMN107 and imatinib (STI571) in patients with imatinib-resistant GIST. This study is designed to determine the Phase II dose of AMN107 and imatinib when administered together in patients with imatinib-resistant GIST, and to characterize the safety, tolerability and pharmacokinetic (PK) profile of this combination.


Eligibility criteria: Inclusion Criteria:

* Patients with gastrointestinal stromal tumor (GIST).
* Patients who have had disease progression during imatinib therapy with 800 mg.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients with prior or concomitant malignancies other than GIST with the exception of previous or concomitant basal cell skin cancer or previous cervical carcinoma in situ.
* A history of impaired cardiac function or uncontrolled cardiovascular disease.
* Severe and/or uncontrolled concurrent disease that could cause unacceptable safety risks such as impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107.
* Currently taking certain medications that could affect an electrocardiogram result.
* Women who are pregnant or breast feeding.
* Patients unwilling or unable to comply with the protocol.

NOTE: Additional inclusion and/ or exclusion criteria may apply.

Primary outcomes:
measure: To determine the MTD which will be the Phase II dose of AMN107 when given in combination with Imatinib. The MTD is defined to be the highest dose of AMN107 in combination with Imatinib given for at least 21 days in the first treatment cycle
timeFrame: From day 1 cycle 1 until at least six subjects have been treated at the recommended dose level and observed for at least 21 days
Secondary outcomes:
measure: To characterize safety and tolerability of AMN107 in combination with Imatinib in GIST
timeFrame: From day 1 cycle to the study completion visit
measure: patients showing progression of disease on Imatinib. The patient will be followed-up for at least 4 cycles (28 days for one cycle)
timeFrame: up to 4 cycles after disease profression on imatinib
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: