Trial Outcomes & Findings for Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma (NCT NCT00045110)

NCT ID: NCT00045110

Last Updated: 2017-08-17

Results Overview

DLT Definition: any grade 3 thrombocytopenia and grade 4 anemia and neutropenia; any non-hematologic grade 3 toxicity; failure to recover from toxicities to be eligible for re-treatment with erlotinib within 2 weeks of the last dose of erlotinib.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 136 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2017-08-17

Participant Flow

Subjects enrolled between August 15, 2002 and August 18, 2005. Patient recruited from outpatient oncology centers.

Participant milestones

Measure	Phase 1 Dose Escalation Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 - Recurrent Malignant Glioma Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are treated with erlotinib as above at the phase II dose. Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose. patients requiring surgery were treated 7 days prior to tumor removal; PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 - Newly Diagnosed GBM Post RT Patients with GBM with newly diagnosed disease following Radiation (RT) started erlotinib no more than 6 weeks from the completion of RT. Temozolomide or other adjuvant chemotherapy not allowed while on erotinib
100mg Phase 1 Dose Escalalation STARTED	6	59	45
100mg Phase 1 Dose Escalalation COMPLETED	6	53	43
100mg Phase 1 Dose Escalalation NOT COMPLETED	0	6	2
200mg Phase 1 Dose Escalation STARTED	4	0	0
200mg Phase 1 Dose Escalation COMPLETED	4	0	0
200mg Phase 1 Dose Escalation NOT COMPLETED	0	0	0
275mg Phase 1 Dose Escalation STARTED	3	0	0
275mg Phase 1 Dose Escalation COMPLETED	3	0	0
275mg Phase 1 Dose Escalation NOT COMPLETED	0	0	0
400mg Phase 1 Dose Escalation STARTED	3	0	0
400mg Phase 1 Dose Escalation COMPLETED	3	0	0
400mg Phase 1 Dose Escalation NOT COMPLETED	0	0	0
525mg Phase 1 Dose Escalation STARTED	3	0	0
525mg Phase 1 Dose Escalation COMPLETED	3	0	0
525mg Phase 1 Dose Escalation NOT COMPLETED	0	0	0
650mg Phase 1 Dose Escalation STARTED	6	0	0
650mg Phase 1 Dose Escalation COMPLETED	6	0	0
650mg Phase 1 Dose Escalation NOT COMPLETED	0	0	0
775mg Dose Escalation STARTED	7	0	0
775mg Dose Escalation COMPLETED	7	0	0
775mg Dose Escalation NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Phase 1 Dose Escalation Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 - Recurrent Malignant Glioma Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are treated with erlotinib as above at the phase II dose. Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose. patients requiring surgery were treated 7 days prior to tumor removal; PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 - Newly Diagnosed GBM Post RT Patients with GBM with newly diagnosed disease following Radiation (RT) started erlotinib no more than 6 weeks from the completion of RT. Temozolomide or other adjuvant chemotherapy not allowed while on erotinib
100mg Phase 1 Dose Escalalation did not initiate treatment	0	2	1
100mg Phase 1 Dose Escalalation prior treatment history	0	4	0
100mg Phase 1 Dose Escalalation ineligible histology	0	0	1

Baseline Characteristics

Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

Baseline characteristics by cohort

Measure	Phase 1 Dose Escalation n=32 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 w/ Recurrent Malignant Glioma n=59 Participants Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib at a predetermined dose (150mg/day). Patients requiring surgery were treated 7 days prior to tumor removal PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis	Phase 2 Newly Diagnosed GBM Post RT n=45 Participants Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose. (150mg/day) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis	Total n=136 Participants Total of all reporting groups
Age, Continuous	45 years n=5 Participants	54 years n=7 Participants	52 years n=5 Participants	52 years n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	25 Participants n=7 Participants	10 Participants n=5 Participants	47 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	34 Participants n=7 Participants	35 Participants n=5 Participants	89 Participants n=4 Participants
Histology Glioblastoma	21 participants n=5 Participants	42 participants n=7 Participants	44 participants n=5 Participants	107 participants n=4 Participants
Histology Anaplastic Astrocytoma	8 participants n=5 Participants	14 participants n=7 Participants	1 participants n=5 Participants	23 participants n=4 Participants
Histology Anaplastic oligodendroglioma	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Histology Atypical meningioma	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Histology Pleomorphic Xanthoastrocytoma	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Histology Oligodendroglioma	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Prior Radiation Treatment Yes	32 participants n=5 Participants	55 participants n=7 Participants	45 participants n=5 Participants	132 participants n=4 Participants
Prior Radiation Treatment No	0 participants n=5 Participants	4 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Prior Number of Chemotherapy Regimens 0 treatments	3 participants n=5 Participants	4 participants n=7 Participants	0 participants n=5 Participants	7 participants n=4 Participants
Prior Number of Chemotherapy Regimens 1 treatment	13 participants n=5 Participants	31 participants n=7 Participants	45 participants n=5 Participants	89 participants n=4 Participants
Prior Number of Chemotherapy Regimens 2 treatments	14 participants n=5 Participants	21 participants n=7 Participants	0 participants n=5 Participants	35 participants n=4 Participants
Prior Number of Chemotherapy Regimens 3 treatments	2 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants
Karnofsky Performance Status Scale	90 units on a scale n=5 Participants	80 units on a scale n=7 Participants	90 units on a scale n=5 Participants	80 units on a scale n=4 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Patients were eligible if they had recurrent disease or if they were newly diagnosed post RT and did NOT have tumor progression (nonprogression glioblastoma) on Enzyme-inducing Antiepileptic Drugs

DLT Definition: any grade 3 thrombocytopenia and grade 4 anemia and neutropenia; any non-hematologic grade 3 toxicity; failure to recover from toxicities to be eligible for re-treatment with erlotinib within 2 weeks of the last dose of erlotinib.

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=32 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 650mg (DVT/PE)	—	—	1 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 150mg (Rash)	—	—	1 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 200mg	—	—	0 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 275mg	—	—	0 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 400mg	—	—	0 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 525mg	—	—	0 dose limiting toxicities	—	—	—	—
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I Dose 775mg (Rash [2])	—	—	2 dose limiting toxicities	—	—	—	—

PRIMARY outcome

Timeframe: cycle 1 - 28 days

Population: Cohorts/dose levels: 150mg; 200mg; 275mg; 400mg; 525mg; 650mg; 775mg patients on Enzyme-inducing Antiepileptic Drugs

standard 3+3 dose escalation design 3 patients in each dose level, observed for 28 days before enrollment to next level. if none of the patients experienced DLT dose escalated, if 1 of 3 experienced DLT 3 more enrolled at that level, if none of the 3 additional pts had DLT escalate to next level, if one or more of the additional pts experienced DLT, the MTD was exceeded and 3 more patients were treated at the next lower dose (if only 3 pts treated at the lower dose). The MTD is the dose at which 0/3 or 1/6 patients have experienced a DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=32 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts	—	—	650 mg	—	—	—	—

PRIMARY outcome

Timeframe: 6 months

Population: 38 Glioblastoma, 15 anaplastic gliomas not receiving Enzyme-inducing Antiepileptic Drugs

Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=53 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II) Recurrent GBM	—	—	2 Participants	—	—	—	—
6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II) Recurrent Anaplastic Glioma	—	—	14 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 1 year

Population: During Cycle 1 only grade 3 severity; patients on Enzyme-inducing Antiepileptic Drugs

CTCAE

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=32 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Percent of Participants With a Grade 3 or 4 Adverse Events Phase 1	—	—	4 Participants	—	—	—	—

SECONDARY outcome

Timeframe: At 1 year

Population: not receiving Enzyme-inducing Antiepileptic Drugs; stable glioblastoma after RT

12 month survival for newly diagnosed stable GBM post RT treated with erlotinib post RT

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=43 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
1 Year Survival - Phase II Newly Diagnosed GBM Post RT	—	—	57 % of participants	—	—	—	—

SECONDARY outcome

Timeframe: 2 years

Population: not receiving Enzyme-inducing Antiepileptic Drugs, glioblastoma stable after RT

Overall Survival defined as Time from Start of treatment to time of death due to any cause

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=45 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Overall Survival Newly Diagnosed GBM Post RT	—	—	14 months Interval 9.0 to 17.0	—	—	—	—

SECONDARY outcome

Timeframe: At 1 year

Population: recurrent malignant gliomas - anaplastic and glioblastoma

Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI

Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined.

Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids.

Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone.

Stable/No Response: Does not qualify for CR, PR, or progression.

Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=48 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II complete response	—	—	1 participants	—	—	—	—
Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II Partial response	—	—	1 participants	—	—	—	—
Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II stable disease	—	—	5 participants	—	—	—	—
Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II Progression	—	—	41 participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: drug related events grade 3-5 CTCAE. 5 patients were not evaluable for response/toxicity.

Summarized by descriptive statistics.

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=99 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Percent of Patients With One or More Grade 3-5 Toxicity Described Based on the CTC Severity Grading Phase II	—	—	29 percent of participants	—	—	—	—

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1.

Population: tmax=time of peak plasma concentration

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg n=4 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg n=1 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg n=6 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg n=5 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Time of Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -	6 h Standard Deviation 0	3.5 h Standard Deviation 3.54	2.3 h Standard Deviation 1.37	2.8 h Standard Deviation 2.2	3.3 h Standard Deviation 1.2	2.2 h Standard Deviation 0.98	2.4 h Standard Deviation 2.07

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

Population: Cp=peak plasma concentration;

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg n=4 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg n=1 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg n=6 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg n=5 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -	487 ng/mL Standard Deviation 0	2327 ng/mL Standard Deviation 1609	603 ng/mL Standard Deviation 160	722 ng/mL Standard Deviation 186	1075 ng/mL Standard Deviation 308	1351 ng/mL Standard Deviation 441	2009 ng/mL Standard Deviation 1133

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

Population: AUC=area under the curve

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg n=4 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg n=1 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg n=6 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg n=5 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Estimation of the Area Under the Curve Per Dose Level Phase I (on Anticonvulsants) -	21.09 ug* h/mL Standard Deviation 0	25.94 ug* h/mL Standard Deviation 21.6	5.33 ug* h/mL Standard Deviation 2.04	7.28 ug* h/mL Standard Deviation 2.54	13.58 ug* h/mL Standard Deviation 2.99	15.77 ug* h/mL Standard Deviation 7.43	18.83 ug* h/mL Standard Deviation 11.9

SECONDARY outcome

Timeframe: cycle 1 day eight

Population: trough level

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg n=2 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg n=4 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg n=1 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg n=6 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg n=5 Participants Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Trough Level Per Dose Level Phase I (on Anticonvulsants) -	634 ng/mL Standard Deviation 0	1356 ng/mL Standard Deviation 132	412 ng/mL Standard Deviation 430	227 ng/mL Standard Deviation 82	821 ng/mL Standard Deviation 154	591 ng/mL Standard Deviation 574	942 ng/mL Standard Deviation 775

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

Population: Cpmax =peak plasma concentration;

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=76 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Peak Plasma Concentration Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -	—	—	872 ng/mL Standard Deviation 399	—	—	—	—

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

Population: tmax=time to peak plasma concentration;

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=76 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Time to Peak Plasma Concentration for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -	—	—	3.0 h Standard Deviation 1.91	—	—	—	—

SECONDARY outcome

Timeframe: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

Population: AUC=area under the curve;

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=76 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Estimation of Area Under the Curve for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg-	—	—	11.86 ug * h/mL Standard Deviation 5.01	—	—	—	—

SECONDARY outcome

Timeframe: One sample on day 8 cycle 1

Population: Cp=peak plasma concentration; tmax=time to Cp; AUC=area under the curve;

plasma concentrations relative to erlotiniab administration and sample time and dose level

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=76 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Trough Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -	—	—	975 ng/mL Standard Deviation 535	—	—	—	—

SECONDARY outcome

Timeframe: Pre-surgery and time of resection

Population: sample 5 and 6 suspected of contamination with blood clot

Drug administered 6 days prior to surgery

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Pharmacokinetics (Plasma) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs	—	—	761 plasma concentration ng/mL Standard Deviation 499	—	—	—	—

SECONDARY outcome

Timeframe: Pre-surgery and time of resection

Population: sample 5 and 6 suspected of contamination with blood clot tumor/tissue concentration

Drug administered 6 days prior to surgery

Outcome measures

Measure	Phase 1 Dose Escalation - 400 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 525 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation n=6 Participants Phase I: Patients concurrently receiving EIAEDs ( on Enzyme-inducing Antiepileptic Drugs ) receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Other: pharmacological study, laboratory biomarker analysis.	Phase 1 Dose Escalation - 200 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 275 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 650 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Phase 1 Dose Escalation - 775 mg Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Pharmacokinetics (Tissue) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs	—	—	497 tumor/tissue concentration ng/g dry weig Standard Deviation 353	—	—	—	—

Adverse Events

Phase 1 Dose Escalation

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Phase 2 Recurrent Malignant Gliomas and Nonprogressive Gbm

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase 1 Dose Escalation n=32 participants at risk Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 Recurrent Malignant Gliomas and Nonprogressive Gbm n=99 participants at risk Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose. patients requiring surgery were treated 7 days prior to tumor removal; PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.
Nervous system disorders seizure	0.00% 0/32 • 2 years	1.0% 1/99 • Number of events 1 • 2 years
Metabolism and nutrition disorders hypomagnesemia	0.00% 0/32 • 2 years	1.0% 1/99 • Number of events 1 • 2 years

Other adverse events

Measure	Phase 1 Dose Escalation n=32 participants at risk Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.	Phase 2 Recurrent Malignant Gliomas and Nonprogressive Gbm n=99 participants at risk Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose. patients requiring surgery were treated 7 days prior to tumor removal; PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.
Skin and subcutaneous tissue disorders rash	59.4% 19/32 • Number of events 19 • 2 years	11.1% 11/99 • Number of events 11 • 2 years
Investigations granulocytopenia	6.2% 2/32 • Number of events 2 • 2 years	0.00% 0/99 • 2 years
Gastrointestinal disorders diarrhea	28.1% 9/32 • Number of events 9 • 2 years	2.0% 2/99 • Number of events 2 • 2 years
General disorders fatigue	15.6% 5/32 • Number of events 5 • 2 years	3.0% 3/99 • Number of events 3 • 2 years
Gastrointestinal disorders nausea	9.4% 3/32 • Number of events 3 • 2 years	0.00% 0/99 • 2 years

Additional Information

Lauren E Abrey, MD

Adult Brain Tumor Consortium

Phone: 410-955-8837

Email: jfisher@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60