Pancreatic Neuroendocrine Tumors
Conditions
Keywords
Neuroendocrine tumors
Brief summary
The purpose of the study is to evaluate the effect of Sunitinib on the clinical benefit response rate.
Interventions
DRUGSunitinib
Sunitinib capsule will be given orally at continuous daily dosing with a dose of 37.5 mg in the morning (regardless fasting or non-fasting, One cycle will be 28days)
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET (Neuroendocrine Tumor)
Exclusion criteria
* Patients with poorly differentiated neuroendocrine cancer are not eligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Response Rate (CBR) | Up to 799 days of treatment | CBR rate is defined as the percentage of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR) ,or stable disease (SD) ≥ 24 weeks. Based on RECIST, CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion. SD is defined neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest dimensions since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 799 days of treatment | ORR is defined as the percentage of participants with a best overall response of confirmed CR or confirmed PR. Based on the response evaluation criteria in solid tumors (RECIST), CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion. |
| Tumor Shrinkage | Up to 799 days of treatment | Tumor shrinkage is defined as the percent change from baseline for the sum of the longest diameter of target lesions in participants. |
| Progression-free Survival (PFS) | Up to 799 days of treatment | PFS is defined as the time from registration to first documentation of progressive disease (PD) or to death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 3 years from the last subject registration to the study | Overall Survival (OS) is defined as the time from registration to documentation of death due to any cause. |
| Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Predose of Cycle 1 Day15, Cycle 2 Day1, Cycle 3 Day1, and Cycle 4 Day 1 | Reference dose is 37.5 mg. Dose-corrected concentration is calculated from the following formula, observed concentration multiplied by 37.5 over actual dose. SU012662 is an active metabolite of sunitinib. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Sunitinib 37.5 mg was orally administered once daily in a continuous daily dosing regimen (1 cycle = 4 weeks). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Met study discontinuation criteria | 1 |
| Overall Study | Objective progression or relapse | 8 |
| Overall Study | Sponsor Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sunitinib |
|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
Primary
Clinical Benefit Response Rate (CBR)
CBR rate is defined as the percentage of participants with a best overall response of confirmed complete response (CR), confirmed partial response (PR) ,or stable disease (SD) ≥ 24 weeks. Based on RECIST, CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion. SD is defined neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest dimensions since the treatment started.
Time frame: Up to 799 days of treatment
Population: Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Clinical Benefit Response Rate (CBR) | 75.0 percentage of participants |
Secondary
Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662).
Reference dose is 37.5 mg. Dose-corrected concentration is calculated from the following formula, observed concentration multiplied by 37.5 over actual dose. SU012662 is an active metabolite of sunitinib.
Time frame: Predose of Cycle 1 Day15, Cycle 2 Day1, Cycle 3 Day1, and Cycle 4 Day 1
Population: The pharmacokinetics analysis set was defined as all participants who had at least one plasma concentration data at trough sampling with steady-state condition. n in the measured values means number of participants analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Sunitinib (Cycle 1 Day 15, n=10) | 53.9 nanogram/mL | Standard Deviation 17.6 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Sunitinib (Cycle 2 Day 1, n=2) | 41.7 nanogram/mL | Standard Deviation 21.9 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Sunitinib (Cycle 3 Day 1, n=8) | 49.9 nanogram/mL | Standard Deviation 19.7 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Sunitinib (Cycle 4 Day 1, n=5) | 53.5 nanogram/mL | Standard Deviation 24.6 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | SU012662 (Cycle 1 Day 15, n=10) | 23.7 nanogram/mL | Standard Deviation 7 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | SU012662 (Cycle 2 Day 1, n=2) | 21.2 nanogram/mL | Standard Deviation 6.36 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | SU012662 (Cycle 3 Day 1, n=8) | 25.7 nanogram/mL | Standard Deviation 9.14 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | SU012662 (Cycle 4 Day 1, n=5) | 19.6 nanogram/mL | Standard Deviation 7.44 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Total drug (Cycle 1 Day 15, n=10) | 77.5 nanogram/mL | Standard Deviation 20.9 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Total drug (Cycle 2 Day 1, n=2) | 62.9 nanogram/mL | Standard Deviation 28.3 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Total drug (Cycle 3 Day 1, n=8) | 75.5 nanogram/mL | Standard Deviation 26.5 |
| Sunitinib | Dose-corrected Trough Plasma Concentrations of Sunitinib, SU012662 and Total Drug (Sunitinib + SU012662). | Total drug (Cycle 4 Day 1, n=5) | 73.0 nanogram/mL | Standard Deviation 28.8 |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of confirmed CR or confirmed PR. Based on the response evaluation criteria in solid tumors (RECIST), CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion.
Time frame: Up to 799 days of treatment
Population: Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Objective Response Rate (ORR) | 50.0 percentage of participants |
Secondary
Overall Survival (OS)
Overall Survival (OS) is defined as the time from registration to documentation of death due to any cause.
Time frame: Up to 3 years from the last subject registration to the study
Population: Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.~OS was not analyzed due to short of events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Overall Survival (OS) | NA Months |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time from registration to first documentation of progressive disease (PD) or to death due to any cause, whichever occurs first.
Time frame: Up to 799 days of treatment
Population: Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication.~Median PFS had not yet been reached due to short of events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Progression-free Survival (PFS) | 16.8 Months |
Secondary
Tumor Shrinkage
Tumor shrinkage is defined as the percent change from baseline for the sum of the longest diameter of target lesions in participants.
Time frame: Up to 799 days of treatment
Population: Full Analysis Set was defined as the population of all enrolled participants in whom well-differentiated pancreatic neuroendocrine tumor had been diagnosed and who received at least one dose of study medication. n in the measured values means number of participants analyzed in the cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Tumor Shrinkage | Cycle 23 (n=4) | -35.1 percent change | Standard Deviation 22.82 |
| Sunitinib | Tumor Shrinkage | Cycle 25 (n=4) | -32.6 percent change | Standard Deviation 19.64 |
| Sunitinib | Tumor Shrinkage | Cycle 27 (n=3) | -30.8 percent change | Standard Deviation 26.68 |
| Sunitinib | Tumor Shrinkage | Cycle 28 (n=2) | -40.4 percent change | Standard Deviation 9.72 |
| Sunitinib | Tumor Shrinkage | Cycle 16 (n=1) | -34.7 percent change | — |
| Sunitinib | Tumor Shrinkage | Cycle 17 (n=5) | -38.7 percent change | Standard Deviation 15.41 |
| Sunitinib | Tumor Shrinkage | Cycle 1 (n=1) | -20.0 percent change | — |
| Sunitinib | Tumor Shrinkage | Cycle 2 (n=11) | -14.4 percent change | Standard Deviation 13.43 |
| Sunitinib | Tumor Shrinkage | Cycle 3 (n=12) | -18.0 percent change | Standard Deviation 17.7 |
| Sunitinib | Tumor Shrinkage | Cycle 5 (n=9) | -26.0 percent change | Standard Deviation 10.03 |
| Sunitinib | Tumor Shrinkage | Cycle 7 (n=9) | -28.5 percent change | Standard Deviation 11.86 |
| Sunitinib | Tumor Shrinkage | Cycle 9 (n=9) | -31.8 percent change | Standard Deviation 17.2 |
| Sunitinib | Tumor Shrinkage | Cycle 11 (n=9) | -36.4 percent change | Standard Deviation 30.11 |
| Sunitinib | Tumor Shrinkage | Cycle 13 (n=9) | -28.8 percent change | Standard Deviation 16.92 |
| Sunitinib | Tumor Shrinkage | Cycle 14 (n=1) | 1.7 percent change | — |
| Sunitinib | Tumor Shrinkage | Cycle 15 (n=7) | -32.5 percent change | Standard Deviation 17.29 |
| Sunitinib | Tumor Shrinkage | Cycle 18 (n=1) | -43.1 percent change | — |
| Sunitinib | Tumor Shrinkage | Cycle 19 (n=4) | -37.8 percent change | Standard Deviation 19.21 |
| Sunitinib | Tumor Shrinkage | Cycle 21 (n=4) | -35.8 percent change | Standard Deviation 19.19 |
| Sunitinib | Tumor Shrinkage | Cycle 29 (n=1) | 3.3 percent change | — |
| Sunitinib | Tumor Shrinkage | Maximum Reduction (n=12) | -34.8 percent change | Standard Deviation 28.76 |