Phase II Study Aiming to Evaluate the Efficacy and Safety of Nilotinib Patients With Gastrointestinal Stromal Tumors (GIST) Resistant or Intolerant to Imatinib and or to 2nd Line Tyrosine Kinas (TK) Inhibitor

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00633295
First received: March 4, 2008
Last updated: January 18, 2011
Last verified: January 2011
  Purpose

The mainstay of therapy for GISTs is surgical resection, however, recurrence is almost inevitable in high-risk tumors and secondary surgery or other salvage therapy has yielded poor outcome. The median survival for patients with unresectable or metastatic GIST is approximately 20 months, and for patients with local recurrence it is 9 to 12 months. Responses to chemotherapy have been at best 5%. The introduction of imatinib has dramatically changed the prognosis of these patients yielding response rates between 41% and 71% and an overall clinical benefit (tumor responses plus stable disease) ranging between 73% and 90%.

However, resistance to imatinib may develop and represents a further clinical challenge. Sunitinib has recently been approved by the FDA for patients whose disease has progressed or who are intolerant to imatinib therapy. Patients with tumor progressing on sunitinib or another 2nd line agent have limited therapeutic alternatives. Reinstitution of imatinib, if possible, is considered an acceptable option for these patients because it may slow the rate of disease progression even in the setting of prior imatinib failure; however a more optimal 3rd line treatment is needed. AMN107 is a novel aminopyrimidine, available as an oral formulation that is ATP -competitive inhibitor of BCR-ABL,more potent than Imatinib. It inhibits proliferation and autophosphorylation of 32 out of 33 BCR-ABL point mutations. In addition AMN107 also inhibits PDGFRα,PDGFRβ, and KIT. Preliminary data from an ongoing Phase I study in imatinib-resistant GIST patients (CAMN107A2103) indicate that AMN107 alone (400 mg BID) and in combination with imatinib (imatinib 400 mg BID plus AMN107 200 mg QD and 400 mg QD) is well tolerated in this pre-treated patients.


Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: AMN107- NILOTINIB
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center Study to Evaluate the Efficacy and Safety of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant or Intolerant to Imatinib and or to 2nd Line Tyrosine Kinas (TK) Inhibitor

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To evaluate the efficacy of nilotinib in GIST patients resistant or intolerant to imatinib and or 2nd line TK inhibitor as measured by tumor up take of FDG PET quantitated by maximum [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the safety and tolerability of nilotinib as measured by rate and severity of adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: June 2008
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nilotinib Drug: AMN107- NILOTINIB
The dose of nilotinib will be 400 mg bid.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Age ≥ 18 years at Visit 1
  • Radiological confirmation of disease progression (CT scan PET-CT, or MRI) during imatinib therapy, on 600- 800 mg per day for at least 6 weeks.
  • Radiological confirmation of disease progression (CT scan or MRI and PET-CT) during 2nd line TK inhibitor therapy.
  • Patients who were intolerant to Imatinib or second line TK inhibitor (like :sunitinib). Intolerance (at any dose and/or duration), is defined as patients who did not progress on imatinib or sunitinib and have discontinued imatinib and or sunitinib therapy due to any ≥ Grade 3 adverse events that persist in spite of optimal supportive care. Patients with Grade 2 adverse events related to imatinib or sunitinib therapy, in spite of optimal supportive care measures, that persist for ≥ one month or that recurs for more than 3 times whether the dose is reduced or discontinued will also qualify patients as intolerant

Exclusion criteria:

  • Prior treatment with nilotinib
  • Treatment with any investigational drug ≤ 4 weeks prior to Visit 1 with the exception of imatinib and sunitinib therapy .

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00633295

Locations
Israel
Novartis Investigative Site
Jerusalem, Israel
Novartis Investigative Site
Tel Aviv, Israel
Novartis Investigative Site
Tel Hashomer, Israel
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00633295     History of Changes
Other Study ID Numbers: CAMN107DIL02
Study First Received: March 4, 2008
Last Updated: January 18, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Novartis:
GIST
TKI
IMATINIB
NILOTINIB
AMN107

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014