Clinical trial NCT00112736
Conditions: Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Diffuse Astrocytoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Pilocytic Astrocytoma Adult Pineal Gland Astrocytoma Adult Subependymal Giant Cell Astrocytoma Recurrent Adult Brain Tumor
Sponsor: National Cancer Institute (NCI)
Start date: 2005-04-01; Completion date: 2014-04-01
Enrollment: 69 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Erlotinib and temsirolimus and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with erlotinib and to see how well they work in treating patients with recurrent malignant glioma.

Detailed description:
PRIMARY OBJECTIVES:

I. To define the maximum tolerated dose (MTD) of OSI-774 (erlotinib; Tarceva) in combination with CCI-779 (temsirolimus) in patients with recurrent malignant glioma who are not taking enzyme-inducing anti-epileptic drugs (EIAEDs). (Phase I) II. To characterize the safety profile of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (Phase I) III. To characterize the pharmacokinetics of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (Phase I) IV. To determine the efficacy of OSI-774 (erlotinib) and CCI-779 (temsirolimus) in patients with recurrent malignant glioma as measured by 6-month progression-free survival. (Phase II)

SECONDARY OBJECTIVES:

I. Overall progression-free survival. (Phase II) II. Response. (Phase II)

TERTIARY OBJECTIVES:

I. To explore the association of response to treatment to the molecular phenotype of the tumor. (Phase II) II. Determine whether OSI-774 (erlotinib) and CCI-779 (temsirolimus) inhibits EGFR and mTOR and the PI3K-AKT-mTOR and RAS-ERK signaling pathways in tumor specimens taken from malignant glioma patients undergoing surgery. (Phase II) III. Tumor concentration of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of temsirolimus followed by a phase II study. Patients are stratified according to study phase (I vs II), histology at study enrollment (glioblastoma multiforme or gliosarcoma vs anaplastic glioma), preoperative candidacy (yes vs no), and presence of measurable or evaluable disease (yes vs no).

PHASE I: Patients receive oral erlotinib once daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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 dose-limiting toxicity.

PHASE II: Patients receive temsirolimus at the MTD and erlotinib as in phase I.

PHASE II (preoperative component): Patients who are surgical candidates may opt to undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these patients receive oral erlotinib once daily until surgery. Patients also receive temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive temsirolimus at the MTD and erlotinib as in phase I.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of the study within 1-8 months. A total of 50 patients (32 patients with glioblastoma multiforme and 18 with anaplastic glioma) will be accrued for the phase II portion of the study within 8-12 months.

Arms: arm 1: PHASE I: Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 (dose escalation). Every 28 days until disease progression or unacceptable toxicity.

pharmacological study: Correlative studies arm 2: Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 at MTD phse I. Every 28 days until disease progression or unacceptable toxicity.

PHASE II (preoperative component): Patients who are surgical candidates may opt to undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these patients receive oral erlotinib once daily until surgery. Patients also receive temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive temsirolimus at the MTD and erlotinib as in phase I.

therapeutic conventional surgery: Undergo surgical resection

laboratory biomarker analysis: Correlative studies
Interventions: intervention 1: erlotinib intervention 2: temsirolimus intervention 3: therapeutic conventional surgery intervention 4: laboratory biomarker analysis intervention 5: pharmacological study
Intervention descriptions: intervention 1: Given orally intervention 2: Given IV intervention 3: Undergo surgical resection intervention 4: Correlative studies intervention 5: Correlative studies

Protocol documents: