Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Sirolimus in Treating Patients With Glioblastoma Multiforme

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI UCLA-0203078 NCI-G02-2114, NCT00047073

Objectives

1. Determine the maximum tolerated dose of sirolimus in patients with glioblastoma multiforme.
2. Determine the safety profile of this drug in these patients.
3. Determine the efficacy of this drug, in terms of 6-month progression-free survival and objective response, in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed intracranial glioblastoma multiforme



• Disease progression by MRI or CT scan
  • Confirmation of true progressive disease (not radiation necrosis) by positron-emission tomography, thallium scanning, MRI, or surgical documentation required if patient received prior interstitial brachytherapy or stereotactic radiosurgery



• Failed prior radiotherapy



• Phase I patients:
  • Eligible for salvage surgery
  • No limits on prior therapy



• Phase II patients:
  • Tumor progression by MRI or CT scan required within the past 14 days if recurrent disease is present
  • No prior therapy for more than 3 relapses
  • Recent resection of recurrent or progressive tumor allowed as long as all of the following conditions apply:
    • Recovered from surgery
    • MRI or CT scan performed no more than 96 hours since prior surgery OR within 4-6 weeks after surgery
    • Baseline MRI or CT scan performed within 14 days of study entry

Prior/Concurrent Therapy:

Biologic therapy

• At least 1 week since prior interferon

Chemotherapy

• At least 2 weeks since prior vincristine
• At least 3 weeks since prior procarbazine
• At least 6 weeks since prior nitrosoureas

Endocrine therapy

• At least 1 week since prior tamoxifen

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy
• At least 1 week since prior noncytotoxic agents (except radiosensitizers)

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 2,000/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT less than 1.5 times ULN

Renal

• Creatinine less than 1.5 mg/dL

Other

• Cholesterol less than 350 mg/dL
• Triglycerides less than 400 mg/dL
• No concurrent disease that would obscure toxicity or dangerously alter drug metabolism
• No other significant uncontrolled serious medical illness that would preclude study participation
• No other cancer except non-melanoma skin cancer or carcinoma in situ of the cervix unless patient is in complete remission and off all therapy for that disease for at least 3 years
• No active infection
• No prior allergic reactions to compounds of similar chemical or biological composition to sirolimus
• No psychiatric illness that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

Expected Enrollment

A total of 3-12 patients will be accrued for phase I of the study within 3-12 months. A total of 32 patients will be accrued for phase II of the study.

Outcomes

Maximum tolerated dose
Safety profile
Efficacy in terms of progression-free survival at 6 months and objective response

Outline

This is a dose-escalation study.

• Phase I: Patients receive oral sirolimus for 5-7 days before surgery. Patients then undergo surgical resection. Patients resume oral sirolimus once daily after full recovery from surgery. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients receive oral sirolimus as in phase I at the dose determined in that phase.

Patients are followed for survival.

Cloughesy TF, Yoshimoto K, Nghiemphu P, et al.: Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5 (1): e8, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Timothy Cloughesy, MD, Protocol chair		Ph: 310-825-5321; 888-798-0719 Email: tcloughesy@mednet.ucla.edu

Registry Information
Official Title		A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme
Trial Start Date		2002-07-18
Registered in ClinicalTrials.gov		NCT00047073
Date Submitted to PDQ		2002-08-08
Information Last Verified		2007-10-19
NCI Grant/Contract Number		CA16042

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