A Phase 1 interventional study of pharmacological study and adjuvant therapy in Adult Giant Cell Glioblastoma, Adult Glioblastoma and Adult Gliosarcoma, sponsored by National Cancer Institute (NCI). Completed at 11 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-04-10.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temsirolimus together with temozolomide and radiation therapy may kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of temsirolimus when administered with temozolomide in combination with radiotherapy followed by adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
II. Assess and describe the adverse events associated with this regimen in these patients.
III. Evaluate the early response to therapy in these patients using an automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging.
SECONDARY OBJECTIVES:
I. Determine the inhibition status of mTOR signaling pathways in peripheral blood mononuclear cells in patients treated with this regimen.
II. Identify potential pharmacokinetic interactions between temozolomide and temsirolimus.
III. Correlate, preliminarily, survival, progression-free survival, and response with pre-treatment tumor tissue molecular markers in these patients.
OUTLINE: This is a multicenter, dose-escalation study of temsirolimus. Patients are assigned to 1 of 2 treatment groups.
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy. Cohorts of 3-6 patients receive escalating doses of temsirolimus 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 a dose-limiting toxicity. At least 6 patients are treated at the MTD.
GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients are evaluated 4-6 weeks after completion of chemoradiotherapy. Patients with stable or responding disease proceed to adjuvant therapy.
ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood collection for immune monitoring and translational/pharmacologic studies. After completion of study treatment, patients are followed periodically for 5 years.
1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.
This study's enrollment of 56 is above the median of 36 across 1,618 interventional studies indexed under Glioblastoma.
Browse Glioblastoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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Inclusion Criteria:
Histologically confirmed glioblastoma multiforme (GBM)
Newly diagnosed disease
No concurrent enzyme-inducing anticonvulsants, including any of the following:
Not receiving warfarin prior to study registration
GROUP 1: (temsirolimus with radiation and temozolomide) Patients receive temsirolimus IV over 30 minutes once weekly. Beginning 7-10 days later, patients also receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. GROUP 2: (radiation and temozolomide) Patients receive oral temozolomide daily and undergo concurrent 3-D conformal radiotherapy or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks. Patients with stable or responding disease proceed to adjuvant therapy. ADJUVANT THERAPY: Beginning 4-6 weeks after the completion of chemoradiotherapy patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study · Procedure: adjuvant therapy · Radiation: 3-dimensional conformal radiation therapy · Radiation: intensity-modulated radiation therapy · Drug: temsirolimus · Drug: temozolomide
Also known as: pharmacological studies
Also known as: 3D conformal radiation therapy, 3D-CRT
Also known as: IMRT
Given IV
Also known as: CCI-779, cell cycle inhibitor 779, Torisel
Given orally
Also known as: SCH 52365, Temodal, Temodar, TMZ
Maximally tolerated dose (MTD), determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Time frame: Up to 24 weeks
Time to treatment related toxicity as assessed by hematologic measures and CTCAE v3.0
Time frame: From registration to documentation of toxicity, up to 5 years
Time to treatment related toxicity greater than grade 3, assessed by CTCAE v3.0
Time frame: From registration to documentation of toxicity, up to 5 years
Time to progression
Time frame: From registration to documentation of progression, up to 5 years
Time to treatment failure
Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals.The effect of dose and ancillary dichotomized covariates such as gender or age (\<50 years versus 50+ years) will be explored using logrank testing involving one covariate at a time.
Time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by patient, up to 5 years
Response to therapy associated with patient outcome, as assessed by automated morphological MRI change detector and physiological MRI techniques, including diffusion-weighted imaging, perfusion-weighted imaging, and chemical shift imaging
Logistic regression and Cox proportional hazards models will be used to determine the association between changes in tumor volume (as assessed by a software package) and tumor response and 12-month survival (logistic regression) and progression-free and overall survival (Cox proportional hazards models).
Time frame: Up to 5 years
This study is completed, as verified in Apr 2013. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)