SOM230 LAR With Bortezomib and Dexamethasone for Refractory or Relapsed Multiple Myeloma
SOM230 LAR With Bortezomib and Dexamethasone for Refractory or Relapsed Multiple Myeloma
The purpose of this study is to determine if adding SOM230 LAR to bortezomib and
 dexamethasone is better than bortezomib and dexamethasone alone and if it should be
 investigated further.
Inclusion Criteria:

 -  Patients must have histologically or cytologically confirmed symptomatic MM,
 Salmon-Durie Stage II or III, International Staging System II or III, or fulfill the
 CRAB criteria (see Appendix A, B). Patients should have previously been treated with
 at least one cycle of bortezomib, after which the patient has shown progressive or
 refractory disease. Finally, patients must meet at least one of the following
 parameters of measurable disease:

 -  Bone marrow plasmacytosis with> 10% plasma cells, or sheets of plasma cells, or
 biopsy proven plasmacytoma which must be obtained within 6 weeks prior to
 registration.

 -  Measurable levels of monoclonal protein (M-protein): ≥ 1 g/dL on serum protein
 electrophoresis (SPEP) or ≥ 200 mg of monoclonal light chain on a 24 hour urine
 protein electrophoresis (UPEP) or involved FLC ≥ mg/dL (≥ 100 mg/L) which must be
 obtained within 4 weeks prior to registration.

 -  Serum and urine M-protein levels should be determined by electrophoresis rather
 than by quantitative immunoglobulin (Ig) measurement. Exceptions are made in
 cases in which the M-spike value may be deemed to be unreliable ( e.g.
 co-migrating M-spike). In these cases, quantitative Ig should be used. To assess
 response and progression, however, SPEP values should only be compared to SPEP
 values and quantitative Ig values only to quantitative Ig values.

 -  Patients must have received at least two prior anti-MM treatments. The prior
 treatments must include at least one IMiD (thalidomide or lenalidomide) and
 bortezomib. If patients are unable to tolerate thalidomide or lenalidomide they can be
 included without prior IMiD treatment. Patients may be included if they did not
 experience grade III neuropathy while on bortezomib. Patients may have previously
 received autologous or peripheral blood stem cell transplantation.

 -  Minimum of four weeks since any major surgery, completion of radiation, or completion
 of all prior systemic anticancer therapy. Exception: e.g. kyphoplasty, vertebroplasty,
 local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high
 risk of pathologic fracture).

 -  Age ≥ 18 years.

 -  Life expectancy of greater than 12 weeks.

 -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%; see
 Appendix B).

 -  Patients must have adequate organ and marrow function as defined below, obtained
 within 4 weeks prior to registration:

 -  Hgb > 9 g/dL (which may be supported by transfusion or growth factors)

 -  Absolute neutrophil count > 1000 x 10-9/L

 -  Platelets ≥ 50,000 x 10-9/L

 -  PT/PTT < 1.5 x upper limits of normal (ULN)

 -  Total bilirubin ≤ 1.5 x (ULN)

 -  Hepatic:

 Serum bilirubin ≤ 1.5 ULN

 Aspartate aminotransferase and alanine aminotransferase

 -  3 × ULN without liver metastases

 -  5 × ULN if documented liver infiltration

 -  Renal:

 Calculated creatinine clearance ≥40 ml/min according to the formula in Appendix D

 -  Cholesterol* ≤ 300 mg/dL

 -  Triglycerides (fasting)* ≤ 2.5 x ULN

 -  Fasting plasma glucose (FPG)** < 1.5X ULN for FPG or HbA1c ≤ 8% *In case one or both
 of these thresholds are exceeded, the patient can only be included after initiation of
 appropriate lipid lowering medication.

 At the principle investigator's discretion, non-eligible patients can be re-screened after
 adequate medical therapy has been instituted.

 -  Patients must not be pregnant or breast feeding and must have a negative pregnancy
 test within 14 days of the administration of the first study treatment. Further, all
 women of childbearing potential and sexually active males must agree to use a
 medically effective contraception method throughout the treatment period and avoid
 conception while participating in this study. Women must not be lactating. Post
 menopausal patients and patients who had a bilateral oophorectomy need not take a
 pregnancy test.

 -  Ability to understand and the willingness to sign a written informed consent document.
 Patient must be informed of the investigational nature of this study.

 -  Patient should be able to swallow pills

 Exclusion Criteria:

 -  Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks
 prior to entering the study or those who have not recovered from AEs due to
 chemotherapy, radiotherapy, or major surgery completed more than 4 weeks prior to
 registration. Exception: local radiation therapy for symptomatic bone lesions (e.g.,
 uncontrolled pain or high risk of pathologic fracture).

 -  Patients with any of the following cardiac abnormalities:

 -  QTcF at screening > 450 msec

 -  History of syncope or family history of idiopathic sudden death

 -  Sustained or clinically significant cardiac arrhythmias

 -  Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, 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

 -  Diabetic patients on antidiabetic medications whose HbA1C > 8%

 -  Patients currently receiving high dose systemic steroids for treatment of MM, patients
 without prior bortezomib treatment, patients who received an investigational agent
 within 5 half lives of the agent.

 -  Patients who require therapeutic (full) anticoagulation such as full dose low
 molecular weight heparin or Coumadin with a goal INR of 2-3.

 -  Patients with known brain metastases (treated or not) will be excluded from this
 clinical trial because of their poor prognosis and because they often develop
 progressive neurologic dysfunction that would confound the evaluation of neurologic
 and other AEs.

 -  Patients with a history of allergic reactions attributed to compounds of similar
 chemical or biologic composition to SOM230 LAR and/or bortezomib or other agents used
 in the study.

 -  Patients should not receive immunization with attenuated live vaccines during study
 period or within 1 week of study entry.

 -  Patients with symptomatic cholelithiasis.

 -  Patients previously treated with sst or sst analogues.

 -  Patients with a second malignancy other than squamous/basal cell carcinoma of the skin
 or in situ carcinoma of the cervix unless the tumor was curatively treated.

 -  Known HIV infection

 -  Patients who have any severe and/or uncontrolled medical conditions or other
 conditions that could affect their participation in the study such as:

 -  Severely impaired lung function

 -  Any active (acute or chronic) uncontrolled disorders

 -  Nonmalignant medical illnesses that are uncontrolled or whose control may be
 jeopardized by the study therapy

 -  Women who are pregnant or breast feeding, or women/men able to conceive and unwilling
 to practice a medically effective method of birth control.

 -  Inability to comply with study and/or follow-up procedures or history of medical
 noncompliance.

 -  Patients who have a serious cardiac condition, such as myocardial infarction within 6
 months, unstable angina, sustained ventricular tachycardia, ventricular fibrillation,
 clinically significant bradycardia, history of syncope, family history of idiopathic
 sudden death, QTc > 450 msec, advanced heart block or heart disease as defined by the
 New York Heart Association Class III or IV. (See ECG guidelines, Section 8.0).

 -  Patients with non-secretory MM.

 -  Patients with prior allogeneic transplantation.