Phase II Study of SOM230 in Patients With Recurrent or Progressive Meningioma
Condition: Cancer
MeSH terms: Meningioma
Intervention: SOM230B
Intervention description: SOM230 is an injectable somatostatin analogue. Like natural somatostatin and other somatostatin analogues (SRIFa), SOM230 exerts its pharmacological activity via binding to somatostatin receptors (sst). There are five known somatostatin receptors: sst 1, 2, 3, 4 and 5. Somatostatin receptors are expressed in different tissues under normal physiological conditions. Somatostatin analogues activate these receptors with different potencies (Schmid and Schoeffter 2004) and this activation results in a reduced cellular activity and inhibition of hormone secretion. Somatostatin receptors are strongly expressed in many solid tumors, especially in neuroendocrine tumors where hormones are excessively secreted e.g. acromegaly (Freda 2002), GEP/NET tumors (Oberg, et al 2004) and Cushing's disease.
Intervention MeSH terms: Pasireotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: meningioma; brain

Summary:

      This is a single-arm, phase II trial of SOM230 in patients with documented recurrent or
      progressive intracranial meningioma who have failed conventional therapy and are not
      candidates for complete surgical resection of their tumors and/or radiation at the time of
      study entry.

      At the time of the final analysis, all patients who are receiving treatment with SOM230 will
      complete the core phase of the study and will continue on the extension phase. During this
      time, additional data on response duration, PFS, and safety will be collected.
    

Eligibility criteria:

        PARTICIPANT SELECTION CRITERIA:

        Inclusion Criteria:

          1. Male or female patients aged 18 years or greater.

          2. Patients with radiographically measurable disease and histologically confirmed
             recurrent or progressive intracranial meningiomas (refer to Appendix 1) who are not
             candidates for complete surgical resection of their tumors because the tumors are in
             eloquent areas of the brain (near critical neural structures)or are not candidates for
             cranial irradiation because a) they have already received radiation or b) the tumor is
             in close proximity to the optic nerve and radiation would likely result in vision
             damage.

          3. Karnofsky Performance Status ≥ 60 (Requires occasional assistance, but is able to care
             for most of his/her personal needs.)

          4. The following labs must not be clinically significant, as determined by PI. (Albumin,
             alkaline phosphatase, calcium, chloride, potassium, total protein, and sodium,)

          5. Serum chemistries are as follows: bilirubin ≤ 1.5 X ULN, ALT or AST ≤ 2.5 X ULN, BUN ≤
             1.5X ULN, creatinine ≤ 1.5 X ULN.

          6. Signed informed consent

        Exclusion Criteria:

          1. Patients receiving any cytotoxic chemotherapy, radiation or immunotherapy within 4
             weeks prior to study enrollment

          2. Patients who have undergone major surgery within 4 weeks(other than diagnostic
             surgery) or have not fully recovered, prior to study enrollment

          3. Patients with malabsorption syndrome, short bowel syndrome, or chologenic diarrhea not
             controlled by specific therapeutic means

          4. Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 1.5 ULN.
             Note: At the principle investigator's discretion, non-eligible patients can be
             re-screened after adequate medical therapy has been instituted.

          5. Patients with symptomatic cholelithiasis

          6. Patients who have congestive heart failure (NYHA Class III or IV), 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.

          7. Patients with congenital QTc syndrome, drug-induced prolonged QTc interval, or QTc
             measurement > 450 msec.

          8. Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic
             persistent hepatitis with serum bilirubin > 1.5 X ULN, and/ or ALT or AST > 2.5 X ULN

          9. Patients with prior or concurrent malignancy except for the following: adequately
             treated basal cell or squamous cell skin cancer, or other adequately treated in situ
             cancer, or any other cancer from which the patient has been disease free for five
             years.

         10. Patients with active or suspected acute or chronic uncontrolled infection or with a
             history of immunocompromise, including a positive HIV test result (ELISA and Western
             blot).

         11. Patients with ANC <1.5 X 109/L; Hgb <10 g/dL; PLT <100 X 109/L

         12. Patients who have any current or prior medical condition that, in the opinion of the
             Investigator, may interfere with the conduct of the study, the evaluation of its
             results, or the rigorous completion of the informed consent process.

         13. Female patients who are pregnant or lactating, or adults of childbearing potential who
             are not practicing a medically acceptable method of birth control. Female patients
             must use barrier contraception in addition to condom use in their partner. If oral
             contraception is used, the patient must have been practicing this method for at least
             two months prior to enrollment and must agree to continue the oral contraceptive
             throughout the course of the study, and for three months after the study has ended.
             Male patients who are sexually active are required to use condoms during the study and
             for three months afterward.

         14. Patients who have participated in any clinical investigation with an investigational
             drug (other than SOM230) within 1 month prior to study drug dosing.

         15. Known hypersensitivity to somatostatin analogues or any component of the pasireotide
             or octreotide LAR or s.c. formulations (see section 6.1.1)

         16. Patients with a history of non-adherence to medical regimens or who are considered
             potentially unreliable or will be unable to complete the entire study

         17. QTcF at screening > 450 msec.

         18. History of syncope or family history of idiopathic sudden death.

         19. Sustained or clinically significant cardiac arrhythmias.

         20. Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac
             failure, clinically significant/symptomatic bradycardia, or high-grade AV block.

         21. 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.

         22. Concomitant medication (s) known to increase the QT interval.