Ph II Study of Perifosine Plus Gleevec for Patients With GIST

Phase 2

Completed

• Conditions: Gastrointestinal Stromal Tumors
• Interventions: Drug: Perifosine; Drug: Imatinib Mesylate

• Registration Number: NCT00455559
• Lead Sponsor: AEterna Zentaris

Brief Summary

This is a Phase II trial designed to determine the efficacy and safety of perifosine plus imatinib mesylate in patients with advanced GIST who develop progressive disease or recurrence while receiving imatinib mesylate.

Detailed Description

This is a Phase II study of perifosine in combination with imatinib mesylate in patients with advanced GIST. Each cycle lasts 28 days. There will be two treatment arms. On both arms, patients will continue the dose of imatinib mesylate taken during the period of disease progression. Patients will be randomized to one either a weekly or a daily perifosine treatment regimen at the time of registration.

Study Timeline

• Study Start: 2006-08
• Study First Submitted: 2007-03-30
• Study First Submitted QC: 2007-03-30
• Study First Posted: 2007-04-03
• Primary Completion: 2010-11
• Study Completion: 2011-10
• Status Verified: 2011-11
• Disposition First Submitted: 2018-02-06
• Disposition First Submitted QC: 2018-02-06
• Disposition First Posted: 2018-02-09
• Last Update Submitted: 2018-02-20
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Perifosine 900 mg/d + imatinib mesylate	Imatinib Mesylate	Perifosine 900 mg/d (300 mg tid), 1 x weekly Oral once-weekly dose of perifosine 900 mg (300 mg tid) + oral daily dose of imatinib mesylate (current dose at time of PD without interruption). Perifosine will be taken on days 1, 8, 15, and 22 of a 28-day cycle. Both medications should be taken with food.
Perifosine 100 mg/d + imatinib mesylate	Imatinib Mesylate	Perifosine 100 mg/d x 28 days Oral daily dose of perifosine 100 mg and oral daily dose of imatinib mesylate (current dose at time of progression of disease \[PD\] without interruption). Both drugs will be taken on a continuous basis and should be taken with food. Each cycle will be defined as 28 days.
Perifosine 100 mg/d + imatinib mesylate	Perifosine	Perifosine 100 mg/d x 28 days Oral daily dose of perifosine 100 mg and oral daily dose of imatinib mesylate (current dose at time of progression of disease \[PD\] without interruption). Both drugs will be taken on a continuous basis and should be taken with food. Each cycle will be defined as 28 days.
Perifosine 900 mg/d + imatinib mesylate	Perifosine	Perifosine 900 mg/d (300 mg tid), 1 x weekly Oral once-weekly dose of perifosine 900 mg (300 mg tid) + oral daily dose of imatinib mesylate (current dose at time of PD without interruption). Perifosine will be taken on days 1, 8, 15, and 22 of a 28-day cycle. Both medications should be taken with food.

Primary Outcome Measures

Name	Time	Method
To determine the efficacy and safety of perifosine plus imatinib mesylate in patients with advanced GIST who develop progressive disease or recurrence while receiving imatinib mesylate.	Every 8 weeks	This is a two-arm Phase II trial to determine whether the experimental regimen is likely to provide a 20% response rate while controlling the toxicity rate at 15%. Response will be evaluated at 2 months from the start of therapy, and is defined using the Choi Criteria. Toxicity is defined as any of the following events: regimen-related death, grade 3 transaminitis, grade 3 gastrointestinal toxicity, or grade 4 fatigue or higher within the same 2-month time window.

Secondary Outcome Measures

Name	Time	Method
To determine whether inhibition of Akt phosphorylation correlates with survival, time to disease progression, or response rate in patients with advanced GIST treated with imatinib mesylate plus perifosine.	Every 8 weeks	As perifosine inhibits activation of Akt and has an acceptable safety profile, this Phase II trial is designed to assess antitumor activity of perifosine in patients with advanced GIST who are refractory to or relapsed from imatinib mesylate.