Ectopic ACTH Syndrome, Nelson Syndrome, Pancreatic Neoplasm, Pituitary Neoplasm
Conditions
Keywords
Rare tumors of neuroendocrine origin, NETs of the pancreatic, Pituitary NETs, EAS Tumors, Nelson's Syndrome, Pancreatic neoplasm, pituitary neoplasm, Nelson Syndrome, ectopic ACTH syndrome, pasireotide LAR, PNETs, PiNETS
Brief summary
This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.
Interventions
DRUGpasireotide LAR
Investigational drug pasireotide LAR was supplied in vials with 20 mg or 40 mg powder and 2 mL vehicle was supplied in ampoules for reconstitution.
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
* Male and Female Patients at least 18 years old * Patient who have rare tumors of neuroendocrine origin, such as tumors of the: 1. pancreas 2. pituitary glands 3. Nelson syndrome 4. ectopic-ACTH secreting tumor * Patients who have failed standard of care treatment or for whom no standard of care treatment exist * Signed Informed Consent
Exclusion criteria
* Patients with active gallbladder disease * Patients with any ongoing or planned anti-neoplastic or interferon therapy * Poorly controlled diabetes mellitus * Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs) | 6 months | The primary efficacy endpoint was defined as the percentage of responders at Month 6 among pooled PNET patients (insulinoma, gastrinoma, VIPoma, and glucagonoma). A responder was defined as a patient who either attained normalization or had a greater than 50% reduction from baseline of the level of the primary biochemical tumor marker at Month 6 (M6). Four insulinoma pts were excluded from analysis because of unavailability of normal ranges for the associated primary biochemical tumor marker (insulin-to-glucose ratio). One patient with VIPoma with a normal baseline was also excluded. As a result, only 20 out of 25 patients with PNET were included in the assessment of the primary endpoint, which was less than the planned sample size of 34. Therefore, the primary objective could not be assessed with sufficient power. Patients with missing Month 6 assessment were considered as non-responders. Responder analyses are reported only for indications with minimum of 6 patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders at Month 6 - Individual NETs | 6 months | Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. |
| Percentage of Responders With Probability of Success at Month 6 - Individual NETs | 6 months | Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. The probability of success was a chance that the true responder rate was greater than 15%) for the indications gastrinoma, prolactinoma, and Nelson's syndrome. |
| PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline, month 6 | Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. One gastrinoma patient had a missing primary tumor marker value at Month 6, but had a Month 5 assessment done on Day 141, which fell within the allowed window period for Month 6. |
| PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline, month 6 | Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. |
| Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline, month 6 | Six patients with Nelson's syndrome met the responder's criteria of attaining normalization or a reduction of more than 50% in primary tumor marker at Month 6. |
Countries
Argentina, Australia, Brazil, Canada, France, Germany, Italy, Mexico, Russia, Spain, Thailand, United States
Participant flow
Recruitment details
For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications.
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide LAR 60mg All patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase. Patients included patients with pancreatic neuroendocrine tumors (PNETs), pituitary NETs (PiNETs), Ectopic ACTH-secreting tumor (EAS) & Nelson's syndrome. | 118 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 |
| Overall Study | Abnormal test procedure result(s) | 3 |
| Overall Study | Administrative problems | 1 |
| Overall Study | Adverse Event | 8 |
| Overall Study | Completed M6/did not enter extension | 27 |
| Overall Study | Discontinued prior to M* | 28 |
| Overall Study | New cancer therapy | 5 |
| Overall Study | Unsatisfactory therapeutic effect | 22 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pasireotide LAR 60mg |
|---|---|
| Age, Continuous | 45.9 Years STANDARD_DEVIATION 14.56 |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 50 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 | 23 / 25 | 71 / 72 | 7 / 7 | 14 / 14 |
| serious Total, serious adverse events | 10 / 25 | 8 / 72 | 5 / 7 | 9 / 14 |
Outcome results
Primary
Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs)
The primary efficacy endpoint was defined as the percentage of responders at Month 6 among pooled PNET patients (insulinoma, gastrinoma, VIPoma, and glucagonoma). A responder was defined as a patient who either attained normalization or had a greater than 50% reduction from baseline of the level of the primary biochemical tumor marker at Month 6 (M6). Four insulinoma pts were excluded from analysis because of unavailability of normal ranges for the associated primary biochemical tumor marker (insulin-to-glucose ratio). One patient with VIPoma with a normal baseline was also excluded. As a result, only 20 out of 25 patients with PNET were included in the assessment of the primary endpoint, which was less than the planned sample size of 34. Therefore, the primary objective could not be assessed with sufficient power. Patients with missing Month 6 assessment were considered as non-responders. Responder analyses are reported only for indications with minimum of 6 patients.
Time frame: 6 months
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Patients with baseline primary biochemical tumor marker levels either missing at baseline or missing ULN or baseline value ≤ ULN were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gastrinoma | Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs) | 46.2 percentage of participants |
| VIpoma | Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs) | 0.0 percentage of participants |
| Glucagonoma | Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs) | 0.0 percentage of participants |
Secondary
Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker
Six patients with Nelson's syndrome met the responder's criteria of attaining normalization or a reduction of more than 50% in primary tumor marker at Month 6.
Time frame: Baseline, month 6
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Responder analysis are reported only for indications with minimum of 6 patients. Patients with missing Month 6 assessment were considered as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gastrinoma | Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline | 6 Participants |
| Gastrinoma | Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Month 6 | 6 Participants |
Secondary
Percentage of Responders at Month 6 - Individual NETs
Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications.
Time frame: 6 months
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gastrinoma | Percentage of Responders at Month 6 - Individual NETs | 46.2 percentage of participants |
| VIpoma | Percentage of Responders at Month 6 - Individual NETs | 21.6 percentage of participants |
| Glucagonoma | Percentage of Responders at Month 6 - Individual NETs | 50.0 percentage of participants |
Secondary
Percentage of Responders With Probability of Success at Month 6 - Individual NETs
Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. The probability of success was a chance that the true responder rate was greater than 15%) for the indications gastrinoma, prolactinoma, and Nelson's syndrome.
Time frame: 6 months
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gastrinoma | Percentage of Responders With Probability of Success at Month 6 - Individual NETs | 46.2 Percentage of participants |
| VIpoma | Percentage of Responders With Probability of Success at Month 6 - Individual NETs | 21.6 Percentage of participants |
| Glucagonoma | Percentage of Responders With Probability of Success at Month 6 - Individual NETs | 50.0 Percentage of participants |
Secondary
PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker
Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6.
Time frame: Baseline, month 6
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Responder analysis are reported only for indications with minimum of 6 patients. Patients with missing Month 6 assessment were considered as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gastrinoma | PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline | 7 Participants |
| Gastrinoma | PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Month 6 | 9 Participants |
Secondary
PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker
Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. One gastrinoma patient had a missing primary tumor marker value at Month 6, but had a Month 5 assessment done on Day 141, which fell within the allowed window period for Month 6.
Time frame: Baseline, month 6
Population: The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Responder analysis are reported only for indications with minimum of 6 patients. Patients with missing Month 6 assessment were considered as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gastrinoma | PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Baseline | 8 Participants |
| Gastrinoma | PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker | Month 6 | 5 Participants |