Carcinoid Tumors
Conditions
Keywords
SOM230, Sandostatin, Carcinoid syndrome
Brief summary
Study evaluating SOM230 in patients with metastatic carcinoid tumors
Interventions
Open label. Patients received starting dose of 300 µg of study drug subcutaneously (s.c.) twice (total of 600 µg ) daily for three days, which could be increased in 150 µg increments up to 900 µg twice daily (total 1800 µg daily) if control of symptoms was not achieved. Prior sponsor agreement was required for a higher dose. A dose of 2400 µg/day was the maximum allowed. Dose reductions of 300 µg/day were allowed at any time if unacceptable toxicity occurred.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with biopsy-proven metastatic carcinoid tumors * Patients with at least one measurable lesion (excluding bone) * Patients must be considered inadequately controlled while on Sandostatin LAR therapy based on the symptoms of carcinoid syndrome (diarrhea and/or flushing) as defined as experiencing a minimum average of at least four bowel movements per day or a minimum average of at least two episodes of flushing per day
Exclusion criteria
* Patients who have been previously treated with certain medications may be required to be without certain medications prior to entering the study * Patients who have undergone major recent surgery / surgical therapy for any cause within 1 month * Patients on any cytotoxic chemotherapy or interferon therapy within the last 2 months * Patients with uncontrolled diabetes mellitus * Patients who had received radiotherapy for any reason within the last 4 weeks must have recovered from any side effects of radiotherapy * Patients who have congestive heart failure unstable angina, cardiac arrhythmia or a history of acute myocardial infarction within the three months preceding enrollment * Patients with chronic liver disease * Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method for birth control. * History of immunocompromise, including a positive HIV test result * Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving SOM230 * Patients who have given a blood donation (of 400 mL or more) within 2 months before receiving SOM230 * Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing * Patients with additional active malignant disease within the last five years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary | 15 days | Complete Symptom Control: an average of ≤ 3 bowel movements per day for at least 15 consecutive days, with no more than 3 episodes on any given day, and no episodes of flushing over the time interval being studied. Partial Symptom Control: an average of \< 4 bowel movements per day for at least 15 consecutive days, with no more than 6 episodes per given day, and an average of fewer than 2 daily flushing episodes over the same given time interval. Treatment failure: Failure to obtain partial or complete treatment success over a consecutive 15-day period at a constant dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Symptom Control (Days) by Dose Class | 15 days | Complete symptom control: an average of three or less bowel movements per day for at least 15 consecutive days, with no more than three episodes on any given day, and no episodes of flushing over the time interval being studied. |
| Duration of Partial Symptom Control (Days) by Dose Class | up to 15 days | Partial symptom control: an average of less than four bowel movements per day for at least 15 consecutive days, with no more than six episodes per any given day, and an average of less than two daily flushing episodes over the same given time interval. |
| The Number of Patients (Participants) With Overall Tumor Response | At least 15 days | The disappearance of all lesions was considered a complete response and at least a 30% decrease in the diameter of lesions was considered a partial response (PR). Progressive disease (PD) required a 20% increase in the sum of the diameters of lesions and changes that did not qualify for PR or PD were considered stable disease. Progression not documented was defined as unknown. No more than a 10% increase in biochemical values, and no clinical signs of DP with complete or adequate control over symptoms were defined as complete treatment success and partial treatment success, respectively. |
| The Overall Safety and Tolerability of Pasireotide | At least 15 days | Safety assessments consisted of recording all AEs and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, vital signs, physical condition and body weight. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide (Any Dose) SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | New Cancer Therapy | 2 |
| Overall Study | Ongoing (After Core) | 7 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Pasireotide (Any Dose) |
|---|---|
| Age Continuous | 61.0 years STANDARD_DEVIATION 8.72 |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Germany | 11 participants |
| Region of Enrollment Netherlands | 4 participants |
| Region of Enrollment Sweden | 5 participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 45 | 20 / 43 | 21 / 31 |
| serious Total, serious adverse events | 3 / 45 | 3 / 43 | 10 / 31 |
Outcome results
Primary
Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary
Complete Symptom Control: an average of ≤ 3 bowel movements per day for at least 15 consecutive days, with no more than 3 episodes on any given day, and no episodes of flushing over the time interval being studied. Partial Symptom Control: an average of \< 4 bowel movements per day for at least 15 consecutive days, with no more than 6 episodes per given day, and an average of fewer than 2 daily flushing episodes over the same given time interval. Treatment failure: Failure to obtain partial or complete treatment success over a consecutive 15-day period at a constant dose level.
Time frame: 15 days
Population: The efficacy analysis population (EAP) consisted of 44 patients all of whom had at least one efficacy assessment available after receiving at least one dose of study drug, but excluded 1 patient who had no post-baseline efficacy assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide (Any Dose) | Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary | Complete symptom control | 3 participants |
| Pasireotide (Any Dose) | Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary | Partial symptom control | 9 participants |
| Pasireotide (Any Dose) | Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary | No control | 32 participants |
Secondary
Duration of Complete Symptom Control (Days) by Dose Class
Complete symptom control: an average of three or less bowel movements per day for at least 15 consecutive days, with no more than three episodes on any given day, and no episodes of flushing over the time interval being studied.
Time frame: 15 days
Population: The efficacy analysis population (EAP) consisted of 44 patients all of whom had at least one efficacy assessment available after receiving at least one dose of study drug, but excluded 1 patient who had no post-baseline efficacy assessments. n= the number of patients with complete symptom control.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pasireotide >900 - ≤1500 μg | Duration of Complete Symptom Control (Days) by Dose Class | 42.0 Days | Standard Deviation 22.68 |
| Pasireotide >1500 - ≤2400 μg | Duration of Complete Symptom Control (Days) by Dose Class | 47.0 Days | — |
| Pasireotide Any Dose | Duration of Complete Symptom Control (Days) by Dose Class | 43.7 Days | Standard Deviation 16.26 |
Secondary
Duration of Partial Symptom Control (Days) by Dose Class
Partial symptom control: an average of less than four bowel movements per day for at least 15 consecutive days, with no more than six episodes per any given day, and an average of less than two daily flushing episodes over the same given time interval.
Time frame: up to 15 days
Population: The efficacy analysis population (EAP) consisted of 44 patients all of whom had at least one efficacy assessment available after receiving at least one dose of study drug, but excluded 1 patient who had no post-baseline efficacy assessments. n= then number of patients with partial sympton control
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pasireotide >900 - ≤1500 μg | Duration of Partial Symptom Control (Days) by Dose Class | 89.8 Days | Standard Deviation 95.77 |
| Pasireotide >1500 - ≤2400 μg | Duration of Partial Symptom Control (Days) by Dose Class | 36.3 Days | Standard Deviation 28.73 |
| Pasireotide Any Dose | Duration of Partial Symptom Control (Days) by Dose Class | 72.0 Days | Standard Deviation 81.58 |
Secondary
The Number of Patients (Participants) With Overall Tumor Response
The disappearance of all lesions was considered a complete response and at least a 30% decrease in the diameter of lesions was considered a partial response (PR). Progressive disease (PD) required a 20% increase in the sum of the diameters of lesions and changes that did not qualify for PR or PD were considered stable disease. Progression not documented was defined as unknown. No more than a 10% increase in biochemical values, and no clinical signs of DP with complete or adequate control over symptoms were defined as complete treatment success and partial treatment success, respectively.
Time frame: At least 15 days
Population: The efficacy analysis population (EAP) consisted of 44 patients all of whom had at least one efficacy assessment available after receiving at least one dose of study drug, but excluded 1 patient who had no post-baseline efficacy assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Complete response for complete treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Partial response for complete treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Stable disease for complete treatment success | 1 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Progressive disease for complete treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Unknown for complete treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Missing for complete treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Complete response for partial treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Partial response for partial treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Stable disease for partial treatment success | 4 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Progressive disease for partial treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Unknown for partial treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Missing for partial treatment success | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Complete response for treatment failure | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Partial response for treatment failure | 0 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Stable disease for treatment failure | 8 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Progressive disease for treatment failure | 10 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Unknown for treatment failure | 1 Participants |
| Pasireotide (Any Dose) | The Number of Patients (Participants) With Overall Tumor Response | Missing for treatment failure | 20 Participants |
Secondary
The Overall Safety and Tolerability of Pasireotide
Safety assessments consisted of recording all AEs and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, vital signs, physical condition and body weight.
Time frame: At least 15 days
Population: The safety population consisted of all patients who received study drug (i.e. who started the pasireotide injections) and was thus identical to the Intent to treat (ITT) population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide (Any Dose) | The Overall Safety and Tolerability of Pasireotide | Death | 1 Participants |
| Pasireotide (Any Dose) | The Overall Safety and Tolerability of Pasireotide | Serious or Significant Events | 23 Participants |
| Pasireotide (Any Dose) | The Overall Safety and Tolerability of Pasireotide | Serious Adverse Events (SAEs) | 14 Participants |
| Pasireotide (Any Dose) | The Overall Safety and Tolerability of Pasireotide | Discontinued due to Adverse Events (AEs) | 12 Participants |