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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Nilotinib

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumors focused on measuring GIST, Imatinib, Sunitinib, Gastrointestinal, Stromal, Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nilotinib

Arm Description

nilotinib 400 mg twice daily (bid).

Outcomes

Primary Outcome Measures

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.

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.

Percent of Patients Achieving Complete Response (CR)

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

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

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 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

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

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.

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.

Full Information

NCT ID

NCT01289028

First Posted

January 16, 2011

Last Updated

November 15, 2016

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01289028

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Stromal Tumors

Keywords

GIST, Imatinib, Sunitinib, Gastrointestinal, Stromal, Tumors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

125 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nilotinib

Arm Type

Experimental

Arm Description

nilotinib 400 mg twice daily (bid).

Intervention Type

Drug

Intervention Name(s)

Nilotinib

Other Intervention Name(s)

AMN107

Primary Outcome Measure Information:

Title

Percent of Patients Achieving Stable Disease (SD)

Description

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.

Time Frame

During the first 4 months

Title

Percent of Patients Achieving Partial Response (PR)

Description

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.

Time Frame

during the first 4 months

Title

Percent of Patients Achieving Complete Response (CR)

Description

Complete response (CR) is the Disappearance of all target lesions.

Time Frame

during the first 4 months

Secondary Outcome Measure Information:

Title

Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population

Description

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 Frame

24 weeks and 52 weeks

Title

Time to Overall Response (CR or PR): Per Protocol Population

Description

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 Frame

24 weeks and 52 weeks

Title

Time to Tumor Progression

Description

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.

Time Frame

during the first 4 months

Title

Duration of Overall Response

Description

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence

Time Frame

during 12 months

Title

Overall Survival, Number of Events Related to Progression of the Disease

Description

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.

Time Frame

during 12 months

Title

Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment.

Description

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.

Time Frame

during 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Bad Saarow

ZIP/Postal Code

155226

Country

Germany

Facility Name

Novartis Investigative Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novartis Investigative Site

City

Duesseldorf

ZIP/Postal Code

40479

Country

Germany

Facility Name

Novartis Investigative Site

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Novartis Investigative Site

City

Frankfurt

ZIP/Postal Code

60488

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Novartis Investigative Site

City

Halle/'Saale

ZIP/Postal Code

06120

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Novartis Investigative Site

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81377

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81675

Country

Germany

Facility Name

Novartis Investigative Site

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

Novartis Investigative Site

City

Bologna

State/Province

BO

ZIP/Postal Code

40138

Country

Italy

Facility Name

Novartis Investigative Site

City

Genova

State/Province

GE

ZIP/Postal Code

16132

Country

Italy

Facility Name

Novartis Investigative Site

City

Taormina

State/Province

ME

ZIP/Postal Code

98039

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

MI

ZIP/Postal Code

20133

Country

Italy

Facility Name

Novartis Investigative Site

City

Padova

State/Province

PD

ZIP/Postal Code

35100

Country

Italy

Facility Name

Novartis Investigative Site

City

Aviano

State/Province

PN

ZIP/Postal Code

33081

Country

Italy

Facility Name

Novartis Investigative Site

City

Torino

State/Province

TO

ZIP/Postal Code

10153

Country

Italy

Gastrointestinal Stromal Tumors

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial