Meningioma
Conditions
Keywords
recurrent intracranial meningioma(s), progressive intracranial meningioma(s)
Brief summary
The purpose of this research study is to evaluate the effectiveness and safety of SOM230C in treating recurrent meningiomas. SOM230C is a newly discovered drug that may stop meningioma cells from growing abnormally. This drug has been used in treatment of other tumors, and information from those other research studies suggests that SOM230C may help to stop the growth of meningiomas.
Detailed description
* To enroll in the study, a sample of the participant's tumor tissue, stored from an earlier study, must be sent to a lab at the Dana-Farber/Harvard Cancer Center for diagnosis and special testing. * Prior to starting the study medication, participants will undergo a Octreotide scan. This is a special type of scan used to obtain information about certain tumors. * Participants will receive the study medication, SOM230C, via an injection into the buttocks every 28 days. Therefore, each treatment cycle lasts 28 days. * The following tests and procedures will be done prior to the first, second and third treatment cycles, and every three treatment cycles thereafter: Complete physical examination including neurological exam; vital signs; current medication and symptom review; blood samples and a pregnancy test (for women of child-bearing potential). * About 2/3 through the first treatment cycle (around day 22), participants will visit the research doctor for a complete physical examination including a neurological exam and blood work. * Participants will have ECGs done prior to their first treatment cycle, about 2/3 through the first and third treatment cycles (around day 22), prior to their sixth treatment cycle, and every three treatment cycles thereafter.
Interventions
DRUGSOM230C
Injection in the buttocks every 28 days
Sponsors
Brigham and Women's Hospital
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Memorial Sloan Kettering Cancer Center
Wake Forest University Health Sciences
Duke University
Cedars-Sinai Medical Center
Northwestern University
Novartis
Patrick Y. Wen, MD
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
* 18 years of age or older * Radiographically measurable disease on contrast-enhanced MRI or CT images * Karnofsky Performance status of 60 or greater * Life expectancy of at least 3 months * Histologically confirmed diagnosis of recurrent or progressive intracranial meningioma(s). This includes benign, atypical, or malignant meningioma; patients with neurofibromatosis type 1 or 2 may participate. Participants without histological confirmation but a classic radiographic picture of meningioma may also enroll. Patients with neurofibromatosis type 2 and a classic radiographic picture of meningioma may also enroll without histological confirmation * At least ten unstained standard (4-5 micron) paraffin slides for immunohistochemistry. Participants who have not had a surgical procedure are exempt from this requirement * Unequivocal evidence for tumor progression by MRI (or CT scan if MRI is contraindicated) * MRI or CT must be performed within 14 days of registration * Patients with malignant meningiomas who require corticosteroids must be on a stable dose for at least 5 days prior to baseline imaging. * For patients who have been treated with external beam radiation, interstitial brachytherapy, or radiosurgery, an interval of 4 or more weeks must have elapses from the completion of radiation therapy to study drug administration, and there must be evidence of tumor progression. * There is no limit on the number of prior therapies
Exclusion criteria
* Any cytotoxic chemotherapy, radiation, immunotherapy, or experimental therapy within 4 weeks prior to study drug administration * Prior therapy with somatostatin, andy somatostatin analogue, or any other hormonal treatment prescribed for the purpose of treating meningioma * Major surgery within 4 weeks prior to study drug administration * Malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means * Poorly controlled diabetes mellitus * Symptomatic cholelithiasis * Congestive heart failure, unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment * QTc \> 450 msec * Risk factors for Torsades de Pointes such as hypokalemia (\< 3.5 mmol/L) not corrected by treatment, hypomagnesemia (\< 0.7 mmol/L or \< 1.6 mg/dL) not corrected by treatment, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block * Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure * Concomitant medication(s) known to increase the QT interval within 4 weeks prior to study drug administration * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis with serum bilirubin \> 2x ULN, serum albumin \< 0.67 LLN, or ALT or AST more than 2 x ULN * Any other primary malignancy within the past 3 years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix) * Active or suspected acute or chronic, uncontrolled infection or any history of immunocompromise, including any positive HIV test result * Abnormal coagulation studies (PT or PTT elevated by 30% above normal limits) * Use of anticoagulant medications (not including anti-platelet medications) * Lab values as specified in the protocol * Any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator * Pregnancy or lactation, or failure to practice a medically acceptable method of birth control * History of alcohol or drug abuse in the 6 month period before study enrollment * Participation in any clinical investigation with an investigational drug within 1 month prior to study drug administration * Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR os s.c. formulations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Month Progression Free Survival | 6 months | Progression is defined using Modified Macdonald Criteria , using a \>/= 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 5 years | Number of participants to experience complete or partial response on study treatment. For response per Modified Macdonald Criteria, all measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. 1. Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids. 2. Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. The steroid dose at the time of the scan evaluation should be no greater than the maximum dose used in the first 8 weeks from initiation of therapy. |
| Treatment-related Events | 5 years | All Grade 3-4-5 adverse events with a treatment attribution of probable, possible or definite based on CTCAE (v3.0) as reported on case report forms |
| Median Progression-Free Survival | 5 years | — |
| Median Time to Progression | 34 months | Per protocol, the study's secondary objectives are to be evaluated for the estimate of median ... PFS ... at time of interest. At this time, all study participants have been followed for progression for a minimum of 34 months (final patient to accrue to study was registered to trial on 06/14/2011), and study manuscript is currently being written-up with this information. |
| Overall Survival | 34 months | Percentage of participants alive 34 months after initiating study treatment. Median Overall Survival has not yet been reached for one study group; therefore, we are reporting Overall Survival rates by the end of the study time frame. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Atypical/Malignant Meningiomas participants with atypical meningiomas (WHO grade 2) or malignant meningiomas (WHO grade 3): patients receive SOM230C (pasireotide LAR) 60 mg intramuscular injections in the buttocks every 28 days | 18 |
| Participants With Benign Meningiomas participants with benign meningiomas (WHO grade 1) or meningiomas with undetermined histology: patients receive SOM230C (pasireotide LAR) 60 mg intramuscular injections in the buttocks every 28 days | 16 |
| Total | 34 |
Baseline characteristics
| Characteristic | Participants With Atypical/Malignant Meningiomas | Participants With Benign Meningiomas | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 28 Participants |
| Age, Continuous | 59 years | 52 years | 54 years |
| KPS scores | 80 percent | 90 percent | 85 percent |
| Race/Ethnicity, Customized Black or African American, Non-Hispanic | 3 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic or Latino (Unknown Race) | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White, Non-Hispanic | 14 participants | 15 participants | 29 participants |
| Race/Ethnicity, Customized White (Unknown Ethnicity) | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 34 |
| serious Total, serious adverse events | 7 / 34 |
Outcome results
Primary
6 Month Progression Free Survival
Progression is defined using Modified Macdonald Criteria , using a \>/= 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Atypical/Malignant Meningiomas | 6 Month Progression Free Survival | 11 percentage of patients |
| Participants With Benign Meningiomas | 6 Month Progression Free Survival | 44 percentage of patients |
Secondary
Median Progression-Free Survival
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Atypical/Malignant Meningiomas | Median Progression-Free Survival | 15 weeks |
| Participants With Benign Meningiomas | Median Progression-Free Survival | 26 weeks |
Secondary
Median Time to Progression
Per protocol, the study's secondary objectives are to be evaluated for the estimate of median ... PFS ... at time of interest. At this time, all study participants have been followed for progression for a minimum of 34 months (final patient to accrue to study was registered to trial on 06/14/2011), and study manuscript is currently being written-up with this information.
Time frame: 34 months
Population: Time to progression only reported for the 32 patients who have progressed (either on treatment or in follow-up).~\[NOTE: The other 2 patients who were treated on study each remain progression-free after \> 1000 days.\]
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With Atypical/Malignant Meningiomas | Median Time to Progression | 124 days |
Secondary
Overall Survival
Percentage of participants alive 34 months after initiating study treatment. Median Overall Survival has not yet been reached for one study group; therefore, we are reporting Overall Survival rates by the end of the study time frame.
Time frame: 34 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Atypical/Malignant Meningiomas | Overall Survival | 45 percentage of participants |
| Participants With Benign Meningiomas | Overall Survival | 73 percentage of participants |
Secondary
Response Rate
Number of participants to experience complete or partial response on study treatment. For response per Modified Macdonald Criteria, all measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. 1. Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids. 2. Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. The steroid dose at the time of the scan evaluation should be no greater than the maximum dose used in the first 8 weeks from initiation of therapy.
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Atypical/Malignant Meningiomas | Response Rate | 0 participants |
| Participants With Benign Meningiomas | Response Rate | 0 participants |
Secondary
Treatment-related Events
All Grade 3-4-5 adverse events with a treatment attribution of probable, possible or definite based on CTCAE (v3.0) as reported on case report forms
Time frame: 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Amylase | 1 events |
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Fatigue | 2 events |
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Hyperglycemia | 8 events |
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Hypoglycemia | 1 events |
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Hypokalemia | 1 events |
| Participants With Atypical/Malignant Meningiomas | Treatment-related Events | Lipase | 3 events |