Neoplasms
Conditions
Keywords
Neoplasms, Carcinoid tumor, Neuroendocrine tumor
Brief summary
Study to allow access to everolimus for patients who are on everolimus treatment in a Novartis-sponsored study and are benefiting from the treatment as judged by the investigator
Detailed description
This multi-center, open-label roll-over study aimed to better characterize the long-term safety of everolimus in subjects currently being treated in a Novartis-sponsored studies and who were receiving clinical benefit on the current study treatment as judged by the Investigator. The study was designed to provide continued treatment with everolimus monotherapy to the subjects. Subjects were allowed to continue combination therapy with Sandostatin LAR® Depot if they were receiving this combination therapy on the parent protocol. Subjects were allowed to continue in this roll-over study until they no longer benefitted from the everolimus treatment as judged by the Investigator, discontinued due to toxicities, subject withdrew consent or lost to follow-up, disease progression, protocol non-compliance, or subject death, whichever occurred first. A subject was considered to have reached end of study when everolimus treatment was permanently discontinued. As per the original protocol, it was designed to collect only serious adverse events (SAEs) and protocol defined adverse events of special interest (AESIs). However, due to the feedback received from health authorities, the protocol was amended in 2016 (3 years after study was initiated) to collect all AEs (non-serious and serious AEs, and AESIs). The protocol was also amended to include an Investigator assessment of clinical benefit at every visit for remaining subjects.
Interventions
DRUGEverolimus
Everolimus was provided by the investigator in 2.5 mg, 5 mg or 10 mg tablets for daily oral administration. The starting dose of everolimus was the same as the last dose that was given in the parent study. Dose modification thereafter was done at the discretion of the Investigator based upon what is in the subject's best interest.
Sandostatin LAR Depot was provided by Novartis or by the investigational site considering local regulations. The dose and frequency of Sandostatin LAR Intramuscular injections was the same as the last dose that was given in the parent study.
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
* Subject enrolled in a Novartis-sponsored, CD&MA study receiving everolimus or everolimus plus Sandostatin LAR Depot and fulfilled all their requirements in the parent study * Subject benefiting from treatment with everolimus, as determined by the guidelines of the parent protocol.
Exclusion criteria
* Subject was permanently discontinued from everolimus study treatment in the parent study. * Subject was receiving everolimus in combination with an unapproved or experimental treatment Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs collected in safety database from enrollment to end of treatment (EOT) plus 30 days, up to approximately 7.2 years. AEs/SAEs collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years | Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. All SAEs were captured in safety database from enrollment. Safety data collection was changed in the protocol amendment released in March 2016: AEs and SAEs were captured in the clinical database from protocol amendment release (18 March 2016). Hence, SAEs from both safety database and clinical database are summarized separately. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Clinical Benefit | After 3 months from enrollment, every 3 months, until end of treatment, assessed up to 7.2 years | Percentage of patients with clinical benefit as judged by the investigator. Investigator attestation of continued clinical benefit was collected in clinical database after protocol amendment (release date 18 March 2016). Clinical benefit assessment before protocol amendment was done retrospectively. |
Countries
Czechia, Italy, Netherlands, Russia, South Korea, Spain, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
There was no screening period. Patients enrolled into trial directly from the parent protocol.
Participants by arm
| Arm | Count |
|---|---|
| Everolimus Participants who were receiving everolimus in a Novartis-sponsored study | 22 |
| Everolimus+Sandostatin LAR Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study | 12 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 0 | 1 |
| Overall Study | Adverse Event | 5 | 5 |
| Overall Study | Disease progression | 15 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Everolimus | Everolimus+Sandostatin LAR | Total |
|---|---|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 9.52 | 57.9 Years STANDARD_DEVIATION 11.3 | 58.4 Years STANDARD_DEVIATION 10.02 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 22 | 2 / 12 | 3 / 34 |
| other Total, other adverse events | 3 / 22 | 5 / 12 | 8 / 34 |
| serious Total, serious adverse events | 6 / 22 | 9 / 12 | 15 / 34 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. All SAEs were captured in safety database from enrollment. Safety data collection was changed in the protocol amendment released in March 2016: AEs and SAEs were captured in the clinical database from protocol amendment release (18 March 2016). Hence, SAEs from both safety database and clinical database are summarized separately.
Time frame: SAEs collected in safety database from enrollment to end of treatment (EOT) plus 30 days, up to approximately 7.2 years. AEs/SAEs collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years
Population: All subjects who received at least one dose of everolimus after enrolling into the roll-over study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs (Clinical Database) | 7 Participants |
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs (Clinical Database) | 2 Participants |
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related SAEs (Clinical Database) | 0 Participants |
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs (Safety database) | 6 Participants |
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related SAEs (Safety database) | 1 Participants |
| Everolimus | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Tretament-related AEs (Clinical Database) | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related SAEs (Clinical Database) | 2 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs (Clinical Database) | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Tretament-related AEs (Clinical Database) | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Treatment-related SAEs (Safety database) | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs (Clinical Database) | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs (Safety database) | 9 Participants |
Secondary
Percentage of Patients With Clinical Benefit
Percentage of patients with clinical benefit as judged by the investigator. Investigator attestation of continued clinical benefit was collected in clinical database after protocol amendment (release date 18 March 2016). Clinical benefit assessment before protocol amendment was done retrospectively.
Time frame: After 3 months from enrollment, every 3 months, until end of treatment, assessed up to 7.2 years
Population: All participants who remained in the study after protocol amendment (18 March 2016) with at least one assessment reported for the specified endpoint
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Everolimus | Percentage of Patients With Clinical Benefit | At 12 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 3 months | 9 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 6 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 9 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 15 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 18 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 21 months | 8 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 24 months | 6 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 27 months | 5 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 30 months | 3 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 33 months | 2 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 36 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 39 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 42 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 45 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 48 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 51 months | 1 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 54 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 57 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 63 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 66 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 69 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 75 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 78 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 81 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 84 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 60 months | 0 Participants |
| Everolimus | Percentage of Patients With Clinical Benefit | At 72 months | 0 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 45 months | 6 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 72 months | 3 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 3 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 48 months | 6 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 6 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 57 months | 5 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 9 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 12 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 51 months | 6 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 15 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 75 months | 3 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 18 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 54 months | 6 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 21 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 84 months | 0 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 24 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 60 months | 5 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 27 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 78 months | 2 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 30 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 63 months | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 33 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 42 months | 6 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 36 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 66 months | 4 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 39 months | 7 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 81 months | 1 Participants |
| Everolimus+Sandostatin LAR | Percentage of Patients With Clinical Benefit | At 69 months | 3 Participants |