CCI-779 in Treating Patients With Recurrent Glioblastoma Multiforme

A Phase II Study of CCI-779 in Patients With Recurrent Glioblastoma Multiforme

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.

Study Overview

• Status: Completed
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: temsirolimus

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
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: temsirolimus; Given IV; Other Names: Torisel; CCI-779; cell cycle inhibitor 779

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients being progression free	Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 18, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Gliosarcoma; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: NCI-2012-01858; U10CA025224 (U.S. NIH Grant/Contract); N997B; CDR0000068623; NCCTG-N997B