Gastrointestinal Stromal Tumors
Conditions
Keywords
GIST, Imatinib, Sunitinib, Gastrointestinal, Stromal, Tumors
Brief summary
This study will evaluate the preliminary efficacy of nilotinib in pretreated patients (Imatinib, Sunitinib) with unresectable or metastatic gastrointestinal stromal tumors.
Interventions
DRUGNilotinib
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Achieving Stable Disease (SD) | During the first 4 months | 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) | during the first 4 months | 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) | during the first 4 months | Complete response (CR) is the Disappearance of all target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Response | during 12 months | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence |
| Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population | 24 weeks and 52 weeks | 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. |
| Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment. | during 12 months | 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. |
| Overall Survival, Number of Events Related to Progression of the Disease | during 12 months | 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 to Overall Response (CR or PR): Per Protocol Population | 24 weeks and 52 weeks | 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 | during the first 4 months | 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. |
Countries
Germany, Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib | 125 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal Lab Value | 1 |
| Overall Study | Adverse Event | 14 |
| Overall Study | Death | 4 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Missing reason for discon | 1 |
| Overall Study | New Cancer Therapy | 2 |
| Overall Study | No longer required | 2 |
| Overall Study | Progressive Disease | 49 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Nilotinib |
|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 12.1 |
| Gender Female | 46 Participants |
| Gender Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 107 / 125 |
| serious Total, serious adverse events | 60 / 125 |
Outcome results
Primary
Percent of Patients Achieving Complete Response (CR)
Complete response (CR) is the Disappearance of all target lesions.
Time frame: during the first 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Percent of Patients Achieving Complete Response (CR) | 0 percentage of participants |
Primary
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.
Time frame: during the first 4 months
Population: ITT set, N=125
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Percent of Patients Achieving Partial Response (PR) | 0 percentage of participants |
Primary
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.
Time frame: During the first 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Percent of Patients Achieving Stable Disease (SD) | 48.8 % participants |
Secondary
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 frame: 24 weeks and 52 weeks
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population | 24 weeks | 92.0 percentage of participants |
| Nilotinib | Analysis of Time to Overall Response (CR or PR) According to RECIST Using Kaplan-Meier Method for ITT Population | 52 weeks | 92.0 percentage of participants |
Secondary
Duration of Overall Response
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence
Time frame: during 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib | Duration of Overall Response | 1331 days |
Secondary
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.
Time frame: during 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Overall Survival, Number of Events Related to Progression of the Disease | 17 events |
Secondary
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.
Time frame: during 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib | Progression Free Survival (PFS) of the Patients Who Were Included Due to an Intolerability of a Prior Treatment. | 110 days |
Secondary
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 frame: 24 weeks and 52 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Time to Overall Response (CR or PR): Per Protocol Population | 24 weeks | 91.2 percentage of participants |
| Nilotinib | Time to Overall Response (CR or PR): Per Protocol Population | 52 weeks | 91.2 percentage of participants |
Secondary
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.
Time frame: during the first 4 months
Population: 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