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

Alternate Title

CCI-779 in Treating Patients With Malignant Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	NABTC-0101 NCT00022724, NABTC-01-01

Objectives

1. Determine the maximum tolerated dose of CCI-779 in patients with malignant glioma.
2. Determine the safety profile of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.
4. Determine the efficacy of this drug, in terms of survival and objective response, in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed intracranial malignant glioma
  • Glioblastoma multiforme
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified



• Initial diagnosis of low-grade allowed, if subsequently progressed



• Recurrent disease must have documented progression by MRI or CT scan



• Progressive disease must have failed prior radiotherapy



• Recent resection of recurrent or progressive tumor allowed provided all of the following are met:
  • Recovered from surgery
  • CT scan or MRI performed no more than 96 hours postoperatively OR at 4-6 weeks postoperatively
  • Concurrent steroid dosage must be stable



• Confirmation of true progressive disease (by PET, thallium scan, MR spectroscopy, or surgical documentation) required after prior interstitial brachytherapy or stereotactic radiosurgery

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
• Phase I:
  • 2 prior chemotherapy regimens allowed
  • 1 prior adjuvant regimen and 1 prior regimen for recurrent or progressive disease

    OR

  • 2 prior regimens for progressive tumor
• Phase II:
  • No more than 1 prior chemotherapy regimen for recurrent malignant glioma
  • No prior chemotherapy allowed for stable glioblastoma multiforme

Endocrine therapy:

• See Disease Characteristics
• At least 1 week since prior tamoxifen

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy for progressive disease
• No more than 1 month since prior radiotherapy for nonprogressive glioblastoma multiforme

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy
• At least 1 week since prior noncytotoxic agents

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 120,000/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
• Cholesterol less than 350 mg/dL
• Triglycerides less than 400 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

Other:

• No active infection
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No significant medical illness that would preclude study
• No disease that would obscure toxicity or dangerously alter drug metabolism
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779 or allergy to or inability to receive antihistamines
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 weeks after study

Expected Enrollment

A total of 36 patients will be accrued for phase I of this study within 12 months. A total of 87 patients will be accrued for phase II of this study within 12 months.

Outline

This is a dose-escalation study. Patients in phase II are stratified according to use of enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no) and disease type (glioblastoma multiforme with stable neuro-imaging after radiotherapy vs recurrent malignant glioma). Patients in phase I must be currently receiving EIAEDs.

• Phase I: Patients receive CCI-779 IV over 30 minutes once weekly. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of CCI-779 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive CCI-779 as in Phase I.

  Patients who are candidates for surgical resection of recurrent disease receive CCI-779 IV over 30 minutes 2 hours prior to surgery and then once weekly, as above, once recovered from surgery.

Patients are followed for survival.

Kuhn JG, Chang SM, Wen PY, et al.: Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma. Clin Cancer Res 13 (24): 7401-6, 2007.[PUBMED Abstract]

Chang SM, Wen P, Cloughesy T, et al.: Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Invest New Drugs 23 (4): 357-61, 2005.[PUBMED Abstract]

Chang SM, Kuhn J, Wen P, et al.: Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs. Invest New Drugs 22 (4): 427-35, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North American Brain Tumor Consortium

Susan Chang, MD, Protocol chair		Ph: 415-353-2966; 800-888-8664 Email: changs@neurosurg.ucsf.edu

Registry Information
Official Title		Phase I/II Trial Of CCI-779 In Patients With Malignant Glioma
Trial Start Date		2001-12-31
Registered in ClinicalTrials.gov		NCT00022724
Date Submitted to PDQ		2001-07-05
Information Last Verified		2005-01-27
NCI Grant/Contract Number		CA62399

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