Patients Completing Core Protocol (CAMN107A2103), Exhibiting Stable Disease (SD), Partial Response (PR) or Complete Response (CR) to Nilotinib in Combination With Imatinib

Study Overview
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Brief Summary
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To provide study drug to patients that benefit from treatment judged by the investigator - to obtain additional long-term safety and efficacy data of this combination regimen in GIST

Official Title
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An Extension to a Phase I Multicenter, Dose Escalation Study of Nilotinib in Combination With Imatinib on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST)

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Nilotinib, Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Documented Complete Response, Partial Response, or Stable Disease at the time of entry to extension study and/or possible benefit from continuing treatment in the view of the investigator. Normal organ and marrow function as defined in core protocol (CAMN107A2103). Extension protocol written informed consent. Exclusion criteria: Inability to swallow the medication. Any unresolved adverse events related to participation in the core protocol (CAMN107A2103). A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits. Other protocol defined inclusion/exclusion criteria may apply.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy: AMN107<br>initial dose of imatinib (dose level 1) was 400 mg bid was administered orally on a continuous daily schedule and was not escalated during the study | Drug: Nilotinib, Imatinib<br>* Nilotinib 50 mg and 200 mg gelatin capsules and Imatinib 100 mg and 400 mg film-coated tablets in bottles.. Medication labels for each study drug complied with the legal requirements of each country, were printed in the local language.<br>|
| Active Comparator: Combination Therapy: AMN107 + Imatinib<br>six possible doses of Nilotinib (100 mg once daily (qd), 200 mg qd, 400 mg qd, 200 mg bid, 300 mg bid, and 400 mg bid). four possible doses of Imatinib (0 mg, 400 mg qd, 600 mg qd, and 400 mg bid).the initial dose of nilotinib (dose level 1) was 200 mg qd and could have been escalated up to 400 mg bid | Drug: Nilotinib, Imatinib<br>* Nilotinib 50 mg and 200 mg gelatin capsules and Imatinib 100 mg and 400 mg film-coated tablets in bottles.. Medication labels for each study drug complied with the legal requirements of each country, were printed in the local language.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of nilotinib either as single agent or in combination with Imatinib | Assessed by AE evaluation, including safety laboratory and cardiac safety (ECG, cardiac enzymes, ECHO) measures. | AE monitored continuously from day 1 cycle 1 to the study completion visit; safety laboratory and cardiac safety monitored every 3 treatment cycles (every 3 months) from day 1 cycle 1 to the study completion visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess any clinical responses in Imatinib-resistant GIST patients. Assessment of tumor response will be made based on modified RECIST criteria - to be assessed at the end of every cycle of treatment | Assessment of tumor response will be made based on modified RECIST criteria. | every 3 months, at completion of every third treatment cycle prior to first dose of next cycle, at study completion visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Cancer, Imatinib-Resistant Gastrointestinal Stromal Tumors, GIST, Nilotinib, Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST)