Pancreatic Neuroendocrine Tumors
Conditions
Brief summary
To evaluate safety and efficacy of everolimus (Afinitor®) in Chinese adult patients with local advanced or metastatic, well differentiated progressive pancreatic neuroendocrine tumors.
Detailed description
This was an open-label, multicenter, single-arm clinical study to evaluate the safety and efficacy of everolimus in Chinese adult patients with locally advanced, unresectable or metastatic, well differentiated progressive pancreatic neuroendocrine tumors. The inclusion and exclusion criteria, as well as the dosing and dose modification criteria are designed according to the approved Chinese Package Insert. The planned sample size of the study was approximately 60 subjects. Subjects who were eligible received the treatment with everolimus provided by sponsor to treat pNET and followed the visit schedule in the protocol to collect safety and efficacy data until progression of disease, unacceptable toxicity, death, protocol deviation or other reason that may lead to discontinuation before the end of study. All subjects were followed-up for survival status every 6 months by the investigator until death, lost to follow-up, withdrawal of consent for survival or end of study. The End of study is defined as either at least 75% of subjects have completed survival follow up or all subjects discontinued study treatment or the last subject finished 5-year survival follow up, whichever comes first. Final analysis was conducted at the end of the study.
Interventions
DRUGeverolimus
Participants were instructed to take everolimus at a starting dose of 10 mg orally once daily. However, dose adjustments were permitted in order to allow the participant to continue the study treatment.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histological confirmed G1 or G2 pancreatic neuroendocrine tumors(pNETs) (WHO 2010) * Patients must have radiological documentation of progression of disease per RECIST 1.1 within 12 months prior to enrollment. * Measurable disease per RECIST 1.1 criteria using triphasic computed tomography (CT) scan or multiphase MRI for radiologic assessment. * everolimus treatment which is recommended by the treating physician
Exclusion criteria
* Hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients. * Patient who is unwilling to receive Afinitor treatment due to any reason. * Pregnant or nursing (lactating) women, * Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus). * Use of an investigational drug within the 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 30 days, up to a maximum duration of approximately 5 years. | Number of participants with treatment emergent adverse events (any AE regardless of seriousness), SAEs, AEs and SAEs on grade 3 or 4, and suspected to be related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 7 years and 6 months. | Overall Survival is defined as the time from the start of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method. |
| Progression Free Survival (PFS) by Investigator Assessment Per RECIST 1.1 | Up to approximately 2 years and 9 months | Progression free survival is defined as the time from the initiation of study treatment to disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier estimates. |
Countries
China
Participant flow
Recruitment details
Participants took part in 5 investigative sites in China.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus Participants were instructed to take everolimus at a starting dose of 10 mg orally once daily. However, dose adjustments were permitted in order to allow the participant to continue the study treatment. | 61 |
| Total | 61 |
Baseline characteristics
| Characteristic | Everolimus |
|---|---|
| Age, Continuous | 53.22 years STANDARD_DEVIATION 14.305 |
| Race/Ethnicity, Customized Asian | 61 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 61 | 22 / 55 |
| other Total, other adverse events | 60 / 61 | 0 / 0 |
| serious Total, serious adverse events | 17 / 61 | 0 / 0 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment emergent adverse events (any AE regardless of seriousness), SAEs, AEs and SAEs on grade 3 or 4, and suspected to be related to the study drug.
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 30 days, up to a maximum duration of approximately 5 years.
Population: Safety Analysis Set (SS): including all participants who received at least one study treatment. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 60 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs-grade 3/4 | 30 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs Suspected to be related to the study drug | 58 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs Suspected to be related to the study drug-grade 3/4 | 19 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 17 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs-grade 3/4 | 11 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs Suspected to be related to the study drug | 8 Participants |
| Everolimus | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs Suspected to be related to the study drug-grade 3/4 | 5 Participants |
Secondary
Overall Survival (OS)
Overall Survival is defined as the time from the start of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method.
Time frame: Up to approximately 7 years and 6 months.
Population: Full Analysis Set (FAS): including all participants who received at least one study treatment. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus | Overall Survival (OS) | 66.56 months |
Secondary
Progression Free Survival (PFS) by Investigator Assessment Per RECIST 1.1
Progression free survival is defined as the time from the initiation of study treatment to disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier estimates.
Time frame: Up to approximately 2 years and 9 months
Population: Full Analysis Set (FAS): including all participants who received at least one study treatment. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus | Progression Free Survival (PFS) by Investigator Assessment Per RECIST 1.1 | 16.07 months |