Study Evaluating SOM230 in Patients With Metastatic Carcinoid Tumors
Study Details
Study Description
Brief Summary
Study evaluating SOM230 in patients with metastatic carcinoid tumors
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pasireotide
|
Drug: Pasireotide (SOM230)
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 2 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
| 3 | Univ. Of Iowa Holden Cancer Center | Iowa City | Iowa | United States | 52242 |
| 4 | Louisiana State University Medical Center | New Orleans | Louisiana | United States | 70112 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CSOM230B2202
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Pasireotide (Any Dose) |
|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Period Title: Overall Study | |
| STARTED | 45 |
| COMPLETED | 17 |
| NOT COMPLETED | 28 |
Baseline Characteristics
| Arm/Group Title | Pasireotide (Any Dose) |
|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Overall Participants | 45 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
61.0
(8.72)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
20
44.4%
|
| Male |
25
55.6%
|
| Region of Enrollment (participants) [Number] | |
| United States |
24
53.3%
|
| Sweden |
5
11.1%
|
| Germany |
11
24.4%
|
| Netherlands |
4
8.9%
|
| France |
1
2.2%
|
Outcome Measures
| Title | Symptom Control (Diarrhea/Flushing) Using a Patient Symptom Diary |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Pasireotide (Any Dose) |
|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Measure Participants | 44 |
| Complete symptom control |
3
6.7%
|
| Partial symptom control |
9
20%
|
| No control |
32
71.1%
|
| Title | Duration of Complete Symptom Control (Days) by Dose Class |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Pasireotide 300 - ≤900 μg | Pasireotide >900 - ≤1500 μg | Pasireotide >1500 - ≤2400 μg | Pasireotide Any Dose |
|---|---|---|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 300 - ≤900 μg / day | SOM230 (Pasireotide), >900 - ≤1500 μg / day | SOM230 (Pasireotide), >1500 - ≤2400 μg / day | SOM230 (Pasireotide), 300 ug - 2400 ug / day |
| Measure Participants | 0 | 2 | 1 | 3 |
| Mean (Standard Deviation) [Days] |
42.0
(22.68)
|
47.0
(NA)
|
43.7
(16.26)
|
| Title | Duration of Partial Symptom Control (Days) by Dose Class |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Pasireotide 300-≤900 μg | Pasireotide >900-≤1500 μg | Pasireotide >1500-≤2400 μg | Pasireotide Any Dose |
|---|---|---|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 450µg twice daily, subcutaneous injection. | SOM230 (Pasireotide), more than 450µg twice daily dose titration up to 750µg twice daily, subcutaneous injection. | SOM230 (Pasireotide), more than 750µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Measure Participants | 0 | 6 | 3 | 9 |
| Mean (Standard Deviation) [Days] |
89.8
(95.77)
|
36.3
(28.73)
|
72.0
(81.58)
|
| Title | The Number of Patients (Participants) With Overall Tumor Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Pasireotide (Any Dose) |
|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Measure Participants | 44 |
| Complete response for complete treatment success |
0
0%
|
| Partial response for complete treatment success |
0
0%
|
| Stable disease for complete treatment success |
1
2.2%
|
| Progressive disease for complete treatment success |
0
0%
|
| Unknown for complete treatment success |
0
0%
|
| Missing for complete treatment success |
0
0%
|
| Complete response for partial treatment success |
0
0%
|
| Partial response for partial treatment success |
0
0%
|
| Stable disease for partial treatment success |
4
8.9%
|
| Progressive disease for partial treatment success |
0
0%
|
| Unknown for partial treatment success |
0
0%
|
| Missing for partial treatment success |
0
0%
|
| Complete response for treatment failure |
0
0%
|
| Partial response for treatment failure |
0
0%
|
| Stable disease for treatment failure |
8
17.8%
|
| Progressive disease for treatment failure |
10
22.2%
|
| Unknown for treatment failure |
1
2.2%
|
| Missing for treatment failure |
20
44.4%
|
| Title | The Overall Safety and Tolerability of Pasireotide |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Pasireotide (Any Dose) |
|---|---|
| Arm/Group Description | SOM230 (Pasireotide), 150µg twice daily dose titration up to 1200µg twice daily, subcutaneous injection. |
| Measure Participants | 44 |
| Death |
1
2.2%
|
| Serious or Significant Events |
23
51.1%
|
| Serious Adverse Events (SAEs) |
14
31.1%
|
| Discontinued due to Adverse Events (AEs) |
12
26.7%
|
Adverse Events
| Time Frame | Up to 2 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population consisted of all patients who received study drug. Dosing began at 150μg twice daily (300μg daily) and went up to 1200μg twice daily (2400μg daily). Through the duration of the study the 45 patients started at 300μg-≤900μg /day, 43 patients proceeded to >900μg-≤1500μg/day and 31 patients proceeded to >1500μg -≤2400μg/day. | |||||
| Arm/Group Title | Pasireotide 300 ≤ 900 μg | Pasireotide > 900 ≤ 1500 μg | Pasireotide > 1500 ≤ 2400 μg | |||
| Arm/Group Description | Pasireotide 300 ≤ 900 μg / day | Pasireotide > 900 ≤ 1500 μg / day | Pasireotide > 1500 ≤ 2400 μg / day | |||
All Cause Mortality |
||||||
| Pasireotide 300 ≤ 900 μg | Pasireotide > 900 ≤ 1500 μg | Pasireotide > 1500 ≤ 2400 μg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Pasireotide 300 ≤ 900 μg | Pasireotide > 900 ≤ 1500 μg | Pasireotide > 1500 ≤ 2400 μg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/45 (6.7%) | 3/43 (7%) | 10/31 (32.3%) | |||
| Cardiac disorders | ||||||
| Tricuspid valve incompetence | 0/45 (0%) | 1/43 (2.3%) | 0/31 (0%) | |||
| Gastrointestinal disorders | ||||||
| Duodenal stenosis | 1/45 (2.2%) | 0/43 (0%) | 0/31 (0%) | |||
| Erosive duodenitis | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Gastritis | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Gastrointestinal haemorrhage | 1/45 (2.2%) | 0/43 (0%) | 0/31 (0%) | |||
| Nausea | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Rectal haemorrhage | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Vomiting | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| General disorders | ||||||
| Oedema peripheral | 1/45 (2.2%) | 0/43 (0%) | 0/31 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic artery embolism | 0/45 (0%) | 0/43 (0%) | 2/31 (6.5%) | |||
| Infections and infestations | ||||||
| Abdominal infection | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Investigations | ||||||
| Lipase increased | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Metabolism and nutrition disorders | ||||||
| Vitamin K deficiency | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Metastatic carcinoid tumour | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Metastatic pain | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Neoplasm progression | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Squamous cell carcinoma | 0/45 (0%) | 1/43 (2.3%) | 0/31 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 0/45 (0%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Venous insufficiency | 0/45 (0%) | 1/43 (2.3%) | 0/31 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Pasireotide 300 ≤ 900 μg | Pasireotide > 900 ≤ 1500 μg | Pasireotide > 1500 ≤ 2400 μg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/45 (53.3%) | 20/43 (46.5%) | 21/31 (67.7%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 3/45 (6.7%) | 0/43 (0%) | 1/31 (3.2%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 8/45 (17.8%) | 7/43 (16.3%) | 2/31 (6.5%) | |||
| Defaecation urgency | 0/45 (0%) | 0/43 (0%) | 2/31 (6.5%) | |||
| Diarrhoea | 2/45 (4.4%) | 3/43 (7%) | 6/31 (19.4%) | |||
| Flatulence | 3/45 (6.7%) | 2/43 (4.7%) | 1/31 (3.2%) | |||
| Nausea | 7/45 (15.6%) | 8/43 (18.6%) | 2/31 (6.5%) | |||
| Steatorrhoea | 0/45 (0%) | 0/43 (0%) | 2/31 (6.5%) | |||
| Vomiting | 2/45 (4.4%) | 2/43 (4.7%) | 2/31 (6.5%) | |||
| General disorders | ||||||
| Fatigue | 6/45 (13.3%) | 2/43 (4.7%) | 7/31 (22.6%) | |||
| Oedema peripheral | 1/45 (2.2%) | 3/43 (7%) | 3/31 (9.7%) | |||
| Infections and infestations | ||||||
| Cystitis | 0/45 (0%) | 0/43 (0%) | 2/31 (6.5%) | |||
| Investigations | ||||||
| Weight decreased | 7/45 (15.6%) | 6/43 (14%) | 6/31 (19.4%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 2/45 (4.4%) | 3/43 (7%) | 3/31 (9.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/45 (0%) | 2/43 (4.7%) | 2/31 (6.5%) | |||
| Back pain | 0/45 (0%) | 3/43 (7%) | 0/31 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 3/45 (6.7%) | 1/43 (2.3%) | 0/31 (0%) | |||
| Dysgeusia | 1/45 (2.2%) | 1/43 (2.3%) | 2/31 (6.5%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
- CSOM230B2202