SOM230 LAR With Bortezomib and Dexamethasone for Refractory or Relapsed Multiple Myeloma

NCT01329289 | Withdrawn Phase 2 DMC

• 1 other identifier: 10-078
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective tumor response

  Responses (CR and PR) and incidence of SD will be tabulated by disease diagnosis. All responses will be reported. Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.

  2 years

Secondary Outcomes (6)

• progression-free survival

  2 years

• Toxicities associated with this investigational combination

  2 years

• Effects of SOM230 LAR on PI3K/MAPK pathway

  2 years

• Effect of bortezomib and SOM230 LAR on RANKL production and OCL formation

  2 years

• IGF-1 inhibition and monitor circulating IGF-1

  2 years

Study Arms (1)

SOM230 with Bortezomib and Dexamethasone

EXPERIMENTAL

Drug: SOM230; Drug: Bortezomib; Drug: Dexamethasone

Interventions

SOM230 DRUG

60 mg intramuscularly (IM) on day 1 of each 28 day cycle

Also known as: Pasireotide

SOM230 with Bortezomib and Dexamethasone

Bortezomib DRUG

1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 of each cycle. Bortezomib will be infused by IV push.

Also known as: Velcade

SOM230 with Bortezomib and Dexamethasone

Dexamethasone DRUG

20 mg orally on day of and day after bortezomib (Days 1, 2, 4, 5, 8, 9, 11, 12).

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex, dexamethasone sodium phosphate, dexamethasone acetate

SOM230 with Bortezomib and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Novartis: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pasireotide; Bortezomib; Dexamethasone; Calcium Dobesilate; dexamethasone 21-phosphate; dexamethasone acetate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2011
• First Posted: April 5, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: February 12, 2016

Record last verified: 2016-02

Locations

US (1)