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

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)

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

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Nilotinib, Imatinib

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy: AMN107; 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; 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.
Active Comparator: Combination Therapy: AMN107 + Imatinib; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: NovartisPharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 26, 2007
• First Submitted That Met QC Criteria: February 27, 2007
• First Posted (Estimate): February 28, 2007

Study Record Updates

• Last Update Posted (Estimate): May 13, 2013
• Last Update Submitted That Met QC Criteria: May 9, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Cancer; Oncology; Nilotinib; GIST; Imatinib-Resistant Gastrointestinal Stromal Tumors; Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CAMN107A2103E1