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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01289028
First received: January 16, 2011
Last updated: September 14, 2016
Last verified: June 2016
  Purpose
This study will evaluate the preliminary efficacy of nilotinib in pretreated patients (Imatinib, Sunitinib) with unresectable or metastatic gastrointestinal stromal tumors.

Condition Intervention Phase
Gastrointestinal Stromal Tumors
Drug: Nilotinib
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center Study to Evaluate the Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percent of Patients Achieving Stable Disease (SD) [ Time Frame: During the first 4 months ] [ Designated as safety issue: No ]
    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.

  • Percent of Patients Achieving Partial Response (PR) [ Time Frame: during the first 4 months ] [ Designated as safety issue: No ]
    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.

  • Percent of Patients Achieving Complete Response (CR) [ Time Frame: during the first 4 months ] [ Designated as safety issue: No ]
    Complete response (CR) is the Disappearance of all target lesions.


Secondary Outcome Measures:
  • Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population [ Time Frame: 24 weeks and 52 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to Overall Response (CR or PR): Per Protocol Population [ Time Frame: 24 weeks and 52 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to Tumor Progression [ Time Frame: during the first 4 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Overall Response [ Time Frame: during 12 months ] [ Designated as safety issue: No ]
    The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence

  • Overall Survival, Number of Events Related to Progression of the Disease [ Time Frame: during 12 months ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment. [ Time Frame: during 12 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 125
Study Start Date: November 2008
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib
nilotinib 400 mg twice daily (bid).
Drug: Nilotinib
Other Name: AMN107

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289028

Locations
Germany
Novartis Investigative Site
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
Italy
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Genova, GE, Italy, 16132
Novartis Investigative Site
Taormina, ME, Italy, 98039
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Padova, PD, Italy, 35100
Novartis Investigative Site
Aviano, PN, Italy, 33081
Novartis Investigative Site
Torino, TO, Italy, 10153
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01289028     History of Changes
Other Study ID Numbers: CAMN107DDE05  2008-000357-35 
Study First Received: January 16, 2011
Results First Received: February 24, 2016
Last Updated: September 14, 2016
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
GIST
Imatinib
Sunitinib
Gastrointestinal
Stromal
Tumors

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Sunitinib
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016