Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.

An Open-label, Multi-center Study to Evaluate the Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.

This study will evaluate the preliminary efficacy of nilotinib in pretreated patients (Imatinib, Sunitinib) with unresectable or metastatic gastrointestinal stromal tumors.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Saarow, Germany, 155226
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40479
    • Novartis Investigative Site
  • Essen, Germany, 45122
    • Novartis Investigative Site
  • Frankfurt, Germany, 60488
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Halle/'Saale, Germany, 06120
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Mannheim, Germany, 68167
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Muenchen, Germany, 81675
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • ME
    • Taormina, ME, Italy, 98039
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10153
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent.
• Radiologically confirmed disease progression during imatinib therapy at a dose of at least 400 mg daily and/or radiologically confirmed disease progression during sunitinib therapy OR documented intolerance to imatinib and/or sunitinib. (Patients with prior additional investigational treatment of GIST prior to study entry can be included.)
• At least one measurable site of disease on CT/MRI as defined by RECIST criteria.

Exclusion Criteria:

• Prior treatment with nilotinib.
• Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1.
• Prior or concomitant malignancies requiring active treatment other than GIST with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ.
• Impaired cardiac function at visit 1
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib; nilotinib 400 mg twice daily (bid).	Drug: Nilotinib; Other Names: AMN107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Achieving Stable Disease (SD)	Neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progression Disease, taking as reference the smallest sum of the longest diameter since the treatment started.	During the first 4 months
Percent of Patients Achieving Partial Response (PR)	The primary efficacy variable was defined as the proportion of patients with a best overall response of CR by Week 16/Month 4 based on local assessment according to RECIST (Version 1.0). This is an at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.	during the first 4 months
Percent of Patients Achieving Complete Response (CR)	Complete response (CR) is the Disappearance of all target lesions.	during the first 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population	Complete Response (CR): Disappearance of all target lesions. and Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.	24 weeks and 52 weeks
Time to Overall Response (CR or PR): Per Protocol Population	Complete Response (CR): Disappearance of all target lesions, and Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.	24 weeks and 52 weeks
Time to Tumor Progression	Time to tumor progression defined as the time from start of treatment to observed tumor progression (censoring for death without progression) as stated in the original protocol was not evaluated as stated in section 9.8.3 of the clinical study report.	during the first 4 months
Duration of Overall Response	The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence	during 12 months
Overall Survival, Number of Events Related to Progression of the Disease	The OS rate could not be calculated due to the high number of censored cases. Number of censored, n (%) 108 (86.4). Only available data is number of events. OS was defined as the time from first study drug administration to death from any cause. If a patient was not known to have died, survival was censored at date of last contact.	during 12 months
Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment.	Progression-free survival (PFS) is defined as the time from first study drug administration to objective tumor progression or death from any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.	during 12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 16, 2011
• First Submitted That Met QC Criteria: February 2, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Estimate): January 2, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Imatinib; Tumors; Gastrointestinal; GIST; Sunitinib; Stromal
• 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
• Other Study ID Numbers: CAMN107DDE05; 2008-000357-35 (EudraCT Number)