CCI-779 in Treating Patients With Recurrent Glioblastoma Multiforme

• ClinicalTrials.gov Identifier: NCT00016328
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: July 18, 2013
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: May 6, 2001
• First Posted Date: January 27, 2003
• Last Update Posted Date: July 18, 2013
• Study Start Date: May 2001
• Actual Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2012)

Percentage of patients being progression free [ Time Frame: 6 months ]

Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 21, 2012)

• Percentage of patients that have not progressed [ Time Frame: 3 months ]
  Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.
• Percentage of patients that have not progressed [ Time Frame: 12 months ]
  Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.
• Percentage of patients that have not progressed [ Time Frame: 18 months ]
  Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.
• Confirmed tumor response defined as an objective status of complete response (CR), partial response (PR), or regression (REGR) on two consecutive evaluations [ Time Frame: Up to 10 years ]
  Ninety-five percent confidence intervals for the true proportion will be calculated using the exact binomial method.
• Time to progression and death [ Time Frame: Up to 10 years ]
  Estimated using Kaplan-Meier. Frequency distributions of baseline patient characteristics will be compared using chi-squared and Wilcoxon tests.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CCI-779 in Treating Patients With Recurrent Glioblastoma Multiforme
• Official Title: A Phase II Study of CCI-779 in Patients With Recurrent Glioblastoma Multiforme
• Brief Summary: Phase II trial to study the effectiveness of CCI-779 in treating patients who have recurrent glioblastoma multiforme. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description

OBJECTIVES:

I. Determine the efficacy of CCI-779, in terms of the percentage of patients who are progression-free at 6 months, time to progression, and time to death, in patients with recurrent glioblastoma multiforme.

II. Determine the toxic effects of this drug in these patients. III. Correlate molecular alterations in the tumors of these patients with response to treatment with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to concurrent P450 anticonvulsant use (yes vs no).

Patients receive CCI-779 IV over 30 minutes once weekly for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 5 years and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study within 39 months.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Recurrent Adult Brain Tumor

Intervention

• Drug: temsirolimus
  Given IV
  Other Names:

  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
• Other: laboratory biomarker analysis
  Correlative studies
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies

Study Arms

Experimental: Treatment (temsirolimus)

Patients receive CCI-779 IV over 30 minutes once weekly for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Interventions:

• Drug: temsirolimus
• Other: laboratory biomarker analysis
• Other: pharmacological study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 21, 2012): 33
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed grade 4 astrocytoma at primary diagnosis or recurrence

  • Gliosarcoma allowed
• Evidence of tumor progression by MRI or CT scan after radiotherapy or first-line chemotherapy
• Measurable or evaluable disease by MRI or CT scan
• Performance status - ECOG 0-2
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL
• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 3 times upper limit of normal
• Creatinine no greater than 2.0 mg/dL
• No myocardial infarction within the past 6 months
• No congestive heart failure requiring ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Cholesterol no greater than 350 mg/dL
• Triglycerides no greater than 400 mg/dL
• Willing to provide correlative laboratory samples
• No uncontrolled infection
• No known hypersensitivity to any components of CCI-779, diphenhydramine hydrochloride, or other similar antihistamines
• No other medical reason that would preclude diphenhydramine premedication
• No other active malignancy
• No other severe disease that would preclude study participation
• Not immunocompromised unless due to corticosteroids
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• See Disease Characteristics
• Prior adjuvant chemotherapy allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No more than 1 prior chemotherapy regimen for recurrent/progressive disease
• No prior polifeprosan 20 with carmustine implant (Gliadel)
• Must be on fixed dose of corticosteroids (or no corticosteroids) at least 1 week prior to baseline scan
• See Disease Characteristics
• At least 12 weeks since prior radiotherapy
• No prior stereotactic radiosurgery or interstitial brachytherapy unless there is a separate lesion on MRI that is outside of the previously treated field
• No prior resection since last chemotherapy or radiotherapy unless there is unequivocal tumor growth on neuro-imaging study since surgery or there is a separate lesion not present in the surgical bed
• More than 4 weeks since prior investigational agents

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT00016328
• Other Study ID Numbers: NCI-2012-01858; N997B; CDR0000068623; NCCTG-N997B; U10CA025224 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: North Central Cancer Treatment Group
• Collaborators: Not Provided

Investigators

• Principal Investigator: Evanthia Galanis; North Central Cancer Treatment Group

• PRS Account: National Cancer Institute (NCI)
• Verification Date: June 2013