IGF-1 Inhibitor Pasireotide Lar in Combination With the m-TOR Inhibitor Everolimus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01234974
Recruitment Status : Withdrawn (Study never undertaken)
First Posted : November 4, 2010
Last Update Posted : January 10, 2013
Information provided by (Responsible Party):
Giampaolo Talamo, Milton S. Hershey Medical Center

Brief Summary:
Observe the safety/tolerability and effectiveness in terms of response rate and duration of response of the combination pasireotide + everolimus in the treatment of patients with relapsed/refractory multiple melanoma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Pasireotide Drug: Everolimus Phase 2

Detailed Description:
Multiple myeloma (MM) is a B-cell malignancy of plasma cells. It represents the second most common hematological malignancy, with non-Hodgkin's lymphoma being the most common.In this protocol, we propose a regimen consisting of a novel combination of two agents with a promising preclinical activity, i.e., pasireotide (IGF-1 inhibitor) and everolimus (mTOR inhibitor), exploring the efficacy of this therapy in patients with MM. We propose enrollment after failure to the first two lines of FDA-approved agents, even in patients who did not have high-dose chemotherapy and SCT. In fact, overall survival after SCT has been shown to be identical when "early" SCT is compared to "late" SCT, i.e., administered at the time of relapse. This provides an important opportunity to test our novel therapeutic approach, reserving SCT for relapse. The advantage of the this strategy is that similar overall survival outcomes can be achieved with fewer patients undergoing SCT. Both everolimus and pasireotide have the potential of being clinically effective against myeloma. A phase II trial of the mTOR inhibitor temsirolimus, an analogue of everolimus, produced a response rate of 38% in relapsed/refractory multiple myeloma. The IGF-1 inhibitor pasireotide is a promising agent, because IGF has been recently found to be one of the most important growth signal molecule in myeloma cells. The combination of everolimus and pasireotide should have a synergistic antimyeloma effect because preclinical data invitro have shown that combined inhibition of mTOR inhibition and IGF-1 led to a synergistic increase of cell growth inhibition in multiple myeloma cells and might represent a potential new treatment strategy.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of the IGF-1 Inhibitor Pasireotide Lar in Combination With the m-TOR Inhibitor Everolimus in Patients With Relapsed/Refractory Multiple Myeloma
Study Start Date : December 2010
Estimated Primary Completion Date : December 2012
Estimated Study Completion Date : December 2013

Arm Intervention/treatment
Experimental: Pasireotide
Pasireotide 60 mg day 1 every 28 days
Drug: Pasireotide
Given as an intramuscular injection on day 1 every 28 days, 60 mg per dose
Other Names:
  • Pasireotide s.c.
  • Pasireotide LAR
  • SOM230
Drug: Everolimus
given as an oral tablet every day on days 1-28, 10 mg per day
Other Name: RAD001

Primary Outcome Measures :
  1. Primary objective [ Time Frame: 12 patients enrolled ]
    Initially 12 patients will be enrolled. If there are no responses among these patients with the combination pasireotide + everolimus in the treatment the study will be terminated.

Secondary Outcome Measures :
  1. Secondary objective [ Time Frame: 25 to 37 patients enrolled ]
    After initial 12 patients enrolled and these patients respond, an additional 25 to 27 patients will be enrolled. We will evaluate efficacy of the combination regimen based primarily on response rate. Progression free-survival and overall survival will also be recorded and analyzed.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically documented multiple myeloma
  • Multiple myeloma relapsing or refractory to at least 2 of the currently accepted therapies for multiple myeloma
  • Age > 18 years
  • Minimum of 4 weeks since any major surgery, radiation or 5 half life since prior systemic anticancer therapy
  • ECOG performance status ≤ 2
  • Anticipated life expectancy of 12 weeks or more
  • Adequate bone marrow function
  • Adequate liver function
  • Calculated creatinine
  • INR ≤ 1.5
  • Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN
  • Women of childbearing potential must have a negative serum pregnancy test. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control during the course of the study.

Exclusion Criteria:

  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
  • Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
  • Patients with prior or concurrent malignancy
  • Patients with uncontrolled diabetes mellitus
  • Patients who have congestive heart failure, unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or history of acute myocardial infarction within the 6 months preceding enrollment.
  • Liver disease
  • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study.
  • Female patients who are pregnant or breast feeding, adults of reproductive potential who are not using effective birth control methods.
  • Male patients whose sexual partner(s) are women of child bering potential and who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment.
  • Patients with a known hypersensitivity to everolimus or other rapamycin or to its excipients.
  • Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol
  • Patients taking medication know to inhibit, induce or be a substrate to isoenzyme CYP3A
  • 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 points, concomitant disease that could prolong QT intervals, use of concomitant medications know to prolong the QT interval.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01234974

United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Principal Investigator: Giampaolo Talamo, MD Milton S. Hershey Medical Center

Responsible Party: Giampaolo Talamo, Associate Professor of Medicine, Milton S. Hershey Medical Center Identifier: NCT01234974     History of Changes
Other Study ID Numbers: PSHCI 09-095
First Posted: November 4, 2010    Key Record Dates
Last Update Posted: January 10, 2013
Last Verified: January 2013

Keywords provided by Giampaolo Talamo, Milton S. Hershey Medical Center:
multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists