Study of AMN107 With Imatinib in Gastrointestinal Stromal Tumors (GIST)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00135005

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

11.8

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: AMN107, STI571	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2005

Actual Primary Completion Date :

Nov 1, 2006

Actual Study Completion Date :

Nov 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMN107 + STI571	Drug: AMN107, STI571

Arm

Intervention/Treatment

Experimental: AMN107 + STI571

Drug: AMN107, STI571

Outcome Measures

Primary Outcome Measures

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 [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]
MTD is defined to be the highest dose of AMN in combination with imatinib given for at least 21 days in the first treatment cycle

Secondary Outcome Measures

To characterize safety and tolerability of AMN107 in combination with Imatinib in GIST [From day 1 cycle to the study completion visit]
patients showing progression of disease on Imatinib. The patient will be followed-up for at least 4 cycles (28 days for one cycle) [up to 4 cycles after disease profression on imatinib]
cycle = 28 days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Boston	Massachusetts	United States	02115
2	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19111-2497
3	Novartis Investigative Site	Lyon Cedex		France	69373
4	Novartis Investigative Site	Berlin		Germany	13125
5	Novartis Investigative Site	Milano	MI	Italy	20133