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

Primary Purpose

Multiple Myeloma

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pasireotide

Everolimus

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Penn State Milton S. Hershey Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pasireotide

Arm Description

Pasireotide 60 mg day 1 every 28 days

Outcomes

Primary Outcome Measures

Primary objective

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

Secondary objective

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.

Full Information

NCT ID

NCT01234974

First Posted

August 24, 2010

Last Updated

January 8, 2013

Sponsor

Milton S. Hershey Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01234974

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Withdrawn

Why Stopped

Study never undertaken

Study Start Date

December 2010 (undefined)

Primary Completion Date

December 2012 (Anticipated)

Study Completion Date

December 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Milton S. Hershey Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

multiple myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pasireotide

Arm Type

Experimental

Arm Description

Pasireotide 60 mg day 1 every 28 days

Intervention Type

Drug

Intervention Name(s)

Pasireotide

Other Intervention Name(s)

Pasireotide s.c., Pasireotide LAR, SOM230

Intervention Description

Given as an intramuscular injection on day 1 every 28 days, 60 mg per dose

Intervention Type

Drug

Intervention Name(s)

Everolimus

Other Intervention Name(s)

RAD001

Intervention Description

given as an oral tablet every day on days 1-28, 10 mg per day

Primary Outcome Measure Information:

Title

Primary objective

Description

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.

Time Frame

12 patients enrolled

Secondary Outcome Measure Information:

Title

Secondary objective

Description

Time Frame

25 to 37 patients enrolled

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giampaolo Talamo, MD

Organizational Affiliation

Milton S. Hershey Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Penn State Milton S. Hershey Medical Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

12. IPD Sharing Statement

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

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