CCI-779 in Treating Patients With Recurrent Glioblastoma Multiforme - Full Text View

Purpose

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.

Condition	Intervention	Phase
Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor	Drug: temsirolimus Other: laboratory biomarker analysis Other: pharmacological study	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of CCI-779 in Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:

Drug Information available for: Sirolimus Everolimus Temsirolimus

Genetic and Rare Diseases Information Center resources: Glioblastoma Gliosarcoma Brain Tumor, Adult Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Percentage of patients being progression free [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Ninety-five percent confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures:

Percentage of patients that have not progressed [ Time Frame: 3 months ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Estimated using Kaplan-Meier. Frequency distributions of baseline patient characteristics will be compared using chi-squared and Wilcoxon tests.


Enrollment:	33
Study Start Date:	May 2001
Primary Completion Date:	August 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016328

Locations


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

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Evanthia Galanis	North Central Cancer Treatment Group

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00016328 History of Changes
Other Study ID Numbers:	NCI-2012-01858 N997B CDR0000068623 NCCTG-N997B U10CA025224
Study First Received:	May 6, 2001
Last Updated:	July 17, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Glioblastoma Brain Neoplasms Gliosarcoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms Nervous System Neoplasms	Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Everolimus Sirolimus Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents

ClinicalTrials.gov processed this record on September 30, 2016