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

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01234974

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

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.

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 Design

Study Type:

Interventional

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 :

Dec 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

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 Names: RAD001

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 Names:

RAD001

Outcome Measures

Primary Outcome Measures

Primary objective [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

Secondary objective [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.