Oral Tarceva Study for Recurrent/Residual Glioblastoma Multiforme and Anaplastic Astrocytoma

• Sponsor: Northwell Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00301418
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 98
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will offer a safe treatment for patients with relapsing recurring glioblastoma (GBM) or anaplastic astrocytoma (AA). The trial will test the hypothesis that Erlotinib (Tarceva, OSI-774) can be safely used up to a dose of 150 mg two times a day for 12 months to ultimately enhance survival of patients with relapsed/refractory GBM/AA. Correlation of response to Tarceva with particular genetic alterations including epidermal growth factor receptor variant type III (EGFRvIII) amplification and phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) loss will be studied.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme; Anaplastic Astrocytoma	Drug: Erlotinib	Phase 1/Phase 2

Detailed Description

The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA, from initial diagnosis, despite multimodal treatment approaches. Initial therapy consists of either surgical resection, external beam radiation or both. The role of adjuvant or concomitant chemotherapy in the initial therapy of GBM and AA has not, as yet, been clearly defined. Since most of these patients experience a recurrence after first-line therapy, improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. In August 2003, the U.S. Food and Drug Administration (FDA) granted orphan drug status for Erlotinib in patients with malignant glioma. Erlotinib (OSI-774) has been shown to be active in a range of tumors including GBM, AA and non small cell lung cancer. Because of the promising results in preliminary studies of Erlotinib and because of significant experience with the safety of the dosages proposed in this study, this study will offer a safe adjuvant treatment for patients with relapsing recurring glioblastoma or anaplastic astrocytoma. Therefore, this phase I/II clinical research trial will test the hypothesis that Erlotinib can be safely used up to a dose of 150 mg bid for 12 cycles to ultimately enhance survival of patients with relapsed/refractory GBM/AA with particular genetic alterations including EGFRvIII amplification and PTEN loss.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Oral Erlotinib (Tarceva, OSI-774) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tarceva (Erlotinib)

Drug: Erlotinib; Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.; Other Names: Tarceva OSI-774

Outcome Measures

Primary Outcome Measures

1. Safety of Twice a Day Oral 150 mg Erlotinib Dosing [duration of the trial]

   Greater than or equal to Grade 2 Adverse Event

Secondary Outcome Measures

1. 6-month Progression Free Survival (PFS) [Duration of the trial]

2. Overall Survival (OS) [Duration of the trial]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female patients of ≥ 18 years of age.

• Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA). All patients will have samples of their tissue evaluated for EGFRvIII overexpression and PTEN loss.

• Patients with a histologically confirmed low grade brain tumor who relapse with an enhancing tumor on magnetic resonance imaging (MRI) can be evaluated for toxicity only.

• Patients must have at least one confirmed and evaluable tumor site.*

*A confirmed tumor site is one which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or computed tomography [CT] scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.

• Patients must have a Karnofsky performance status ≥ 60% (or the equivalent Eastern Cooperative Oncology Group [ECOG] level of 0-2) and an expected survival of ≥ three months.

• No chemotherapy for six weeks prior to treatment under this research protocol and no external beam radiation for eight weeks prior to treatment under this research protocol.

• Patients must have adequate hematologic reserve with WBC ≥ 3000/mm3, absolute neutrophils ≥ 1500/mm3 and platelets ≥ 100,000/mm3. Patients who are on Coumadin must have a platelet count of ≥ 150,000/mm3

• Pre-enrollment chemistry parameters must show: bilirubin < 1.5X the institutional upper limit of normal (IUNL); AST or ALT < 2.5X IUNL and creatinine < 1.5X IUNL.

• Pre-enrollment coagulation parameters (PT and PTT) must be ≤ 1.5X the IUNL.

• Concomitant Medications:

• Growth factor(s): Must not have received within 1 week of entry onto this study.

• Steroids: Systemic corticosteroid therapy is permissible in patients with centrail nervous system (CNS) tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.

• Study Specific: Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme inducing anticonvulsants or will not be allowed on this study. Patients receiving proton pump inhibitor or H2 blockers will not be allowed on study. Patients taking antacids will be allowed on study although they should not take the antacid for two hours before or two hours after taking erlotinib.

• Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.

• Patients should not have received a CYP3A4 inhibitor within 1 week of study entry and should not have received a CYP3A4 inducer within 4 weeks of study entry.

• Patients should not have received proton-pump inhibitors within 5 days of study entry or H2 blockers within 2 days of study entry.

• Patients on steroids must receive prophylaxis for Pneumocystis carinii pneumonia (PCP) with Bactrim, unless they have a history of allergy to sulfa drugs.

• Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening.

Exclusion Criteria:

• Previous treatment with Tarceva®.

• Women who are pregnant or lactating.

• Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.

• Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lenox Hill Brain Tumor Center	New York	New York	United States	10075

Sponsors and Collaborators

• Northwell Health
• Genentech, Inc.

Investigators

• Principal Investigator: John A Boockvar, M.D., Feinstein Institute for Medical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

• Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005 Nov 10;353(19):2012-24. Erratum in: N Engl J Med. 2006 Feb 23;354(8):884.

• Responsible Party: John A. Boockvar, Professor, Northwell Health
• ClinicalTrials.gov Identifier: NCT00301418
• Other Study ID Numbers: 501007705
• First Posted: Mar 10, 2006
• Last Update Posted: Feb 10, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by John A. Boockvar, Professor, Northwell Health: Glioblastoma Multiforme; Anaplastic Astrocytoma; High Grade Glial Neoplasms; Brain Tumor
• Additional relevant MeSH terms: Glioblastoma; Astrocytoma; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (10.7)
Sex: Female, Male (Count of Participants)
Female	4 36.4%
Male	7 63.6%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Safety of Twice a Day Oral 150 mg Erlotinib Dosing
Description	Greater than or equal to Grade 2 Adverse Event
Time Frame	duration of the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
Measure Participants	11
Number [participants]	9 81.8%

2. Secondary Outcome

Title	6-month Progression Free Survival (PFS)
Time Frame	Duration of the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
Measure Participants	11
Median (95% Confidence Interval) [days]	56

3. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	Duration of the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
Measure Participants	11
Median (95% Confidence Interval) [days]	167

Adverse Events

Arm/Group Title	Tarceva (Erlotinib)
Arm/Group Description	Erlotinib: Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
All Cause Mortality
	Tarceva (Erlotinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tarceva (Erlotinib)
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Tarceva (Erlotinib)
	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)
Gastrointestinal disorders
Diarrhea	6/11 (54.5%)
Skin and subcutaneous tissue disorders
Rash	9/11 (81.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.