Clinical Trial: Temsirolimus and Perifosine in Treating Patients With Recurrent or Progressive Malignant Glioma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I/II Trial of Temsirolimus and Perifosine for Recurrent or Progressive Malignant Gliomas

Brief Summary: This phase I/II trial studies the side effects and best dose of temsirolimus when given together with perifosine and to see how well it works in treating patients with recurrent or progressive malignant glioma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as perifosine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with perifosine may be an effective treatment for malignant glioma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Define the maximum tolerated dose (MTD) of temsirolimus in combination with perifosine in patients with recurrent or progressive malignant glioma who are not taking enzyme-inducing anti-epileptic drugs (EIAEDs). (Phase I) II. Determine the efficacy of temsirolimus in combination with perifosine in patients with recurrent/progressive glioblastomas (GBMs) not taking EIAEDs as measured by 6 month progression-free survival (6mPFS) and radiographic response rates. (Phase II)

SECONDARY OBJECTIVES:

I. Characterize the safety profile of perifosine and temsirolimus. II. Estimate median overall and progression-free survival. III. Explore the association of pre-treatment molecular phenotype with response to treatment.

IV. Explore molecular effects during treatment including phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (S6K) and rat sarcoma (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) signaling, proliferation, and apoptosis.

OUTLINE: This is a phase I dose-escalation study of temsirolimus, followed by a phase II study.

PHASE I: Patients receive temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22 and perifosine orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive temsirolimus and perifosine as in phase I. Some patients may also undergo cytoreductive surgery.

After com
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum Tolerated Dose of Temsirolimus [ Time Frame: 28 days ]
    MTD defined as the dose at which fewer than one-third of patients experience a dose limiting toxicity (DLT) according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
  • Determine the Efficacy of Temsirolimus in Combination With Perifosine in Patients With Recurrent/Progressive Glioblastomas (GBMs) Not Taking EIAEDs as Measured by 6 Month Progression-free Survival (6mPFS) and Radiographic Response Rates. (Phase II) [ Time Frame: 5 years ]
    This data has yet to be analyzed.


Original Primary Outcome:

  • Maximum tolerated dose of temsirolimus in combination with perifosine (Phase I)
  • Progression-free survival at 6 months (Phase II)
  • Radiographic response rate (Phase II)


Current Secondary Outcome:

Original Secondary Outcome:

  • Toxicity
  • Overall survival
  • Progression-free survival
  • Molecular effects during treatment
  • Molecular predictors of response


Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 15, 2010
Date Started: January 2010
Date Completion:
Last Updated: April 13, 2017
Last Verified: November 2016