Gastrointestinal Stromal Tumor (GIST)
Conditions
Keywords
Unresectable GIST, metastatic GIST, nilotinib, AMN107, imatinib, STI571
Brief summary
This study will evaluate efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed diagnosis of GIST which is unresectable and/or metastatic and either: * have not received any prior anti-neoplastic therapy other than adjuvant imatinib. Note: newly diagnosed patients may have received up to 14 days of treatment with imatinib for disease management while awaiting entry to the study or * recurrent GIST after stopping adjuvant treatment with imatinib and no subsequent treatment with any other therapies. 2. At least one measurable site of disease on CT/MRI scan 3. Performance status ≤ 2 (capable of self-care but unable to carry out any work) 4. Normal organ, electrolyte and marrow function
Exclusion criteria
1. Any prior anti-neoplastic therapy with the exception of patients who have received adjuvant imatinib or patients with newly diagnosed metastatic/ unresectable GIST whose disease requires therapy while awaiting entry to the study. 2. Disease progression during adjuvant therapy with imatinib 3. History of active malignancy (other than GIST) within 10 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ. 4. Impaired cardiac function Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression Free Survival (PFS) | up to month 37 | PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Denmark, Egypt, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Venezuela
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imatinib First, Then Nilotinib patients were on imatinib 400mg once daily in the core phase and then crossed over to nilotinib 400 mg twice a day in the extension phase | 324 |
| Nilotinib First, Then Imatinib patients were on nilotinib 400 mg twice a day in the core phase and then crossed over to in the extension phase imatinib 400mg once daily | 320 |
| Total | 644 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Phase up to 36 Months | Abnormal laboratory value | 1 | 0 |
| Core Phase up to 36 Months | Abnormal test procedure result | 2 | 2 |
| Core Phase up to 36 Months | Administrative problems | 3 | 3 |
| Core Phase up to 36 Months | Adverse Event | 31 | 21 |
| Core Phase up to 36 Months | Death | 5 | 8 |
| Core Phase up to 36 Months | Disease progression | 139 | 119 |
| Core Phase up to 36 Months | Lost to Follow-up | 3 | 7 |
| Core Phase up to 36 Months | Patients didn't receive 1st line therapy | 3 | 4 |
| Core Phase up to 36 Months | Protocol deviation | 5 | 6 |
| Core Phase up to 36 Months | Study terminated by sponsor | 116 | 133 |
| Core Phase up to 36 Months | Withdrawal by Subject | 16 | 17 |
| Optional Extension Phase | Administrative problems | 2 | 0 |
| Optional Extension Phase | Adverse Event | 4 | 5 |
| Optional Extension Phase | Death | 1 | 5 |
| Optional Extension Phase | Disease progression | 22 | 70 |
| Optional Extension Phase | Lost to Follow-up | 1 | 0 |
| Optional Extension Phase | Protocol deviation | 0 | 2 |
| Optional Extension Phase | Study terminated by sponsor | 3 | 37 |
| Optional Extension Phase | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Imatinib First, Then Nilotinib | Nilotinib First, Then Imatinib | Total |
|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 12.91 | 57.3 years STANDARD_DEVIATION 12.63 | 57.35 years STANDARD_DEVIATION 12.77 |
| Sex: Female, Male Female | 145 Participants | 133 Participants | 278 Participants |
| Sex: Female, Male Male | 179 Participants | 187 Participants | 366 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 291 / 321 | 289 / 316 | 28 / 39 | 89 / 125 |
| serious Total, serious adverse events | 80 / 321 | 85 / 316 | 15 / 39 | 26 / 125 |
Outcome results
Primary
Time to Progression Free Survival (PFS)
PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: up to month 37
Population: Full Analysis Set (FAS) consists of all randomized patients for the Core Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib | Time to Progression Free Survival (PFS) | 25.9 months |
| Imatinib | Time to Progression Free Survival (PFS) | 29.7 months |
p-value: 0.008195% CI: [1.104, 1.945]Hazard Ratio