Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma
This study is currently recruiting participants.
Verified March 2012 by Comprehensive Cancer Center of Wake Forest University

First Received on April 13, 2010.  
Last Updated on March 9, 2012  
History of Changes
Sponsor: Comprehensive Cancer Center of Wake Forest University
Collaborator: National Cancer Institute (NCI)
Information provided by (Responsible Party): Comprehensive Cancer Center of Wake Forest University Identifier: NCT01103375

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given with isotretinoin in treating patients with recurrent malignant glioma. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help cells that are involved in the body’s immune response to work better. Giving erlotinib hydrochloride together with isotretinoin may kill more tumor cells

Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Diffuse Astrocytoma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Adult Oligodendroglioma
Recurrent Adult Brain Tumor
Drug: erlotinib hydrochloride
Drug: isotretinoin
Other: laboratory biomarker analysis
Genetic: protein expression analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Single Arm Open Label Study of Erlotinib and 13-cis-Retinoic Acid (CRA) in Patients With Recurrent Malignant Gliomas

Resource links provided by NLM:

Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:

  • Recommended phase II doses of erlotinib hydrochloride and isotretinoin [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    At least 3 patients will be treated at each dose level and the maximum tolerated dose (MTD) will be determined. Patients will be evaluated for dose-limiting toxicity (DLT) in the first 3 weeks on protocol.

Secondary Outcome Measures:

  • Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Response rates (complete or partial response) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples [ Time Frame: Pre-study ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2010
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)


Assigned Interventions
Experimental: Treatment (enzyme inhibitor, immunotherapy)

Patients receive isotretinoin PO QD on days 1-21 and erlotinib hydrochloride PO QD on days 1-28.
Drug: erlotinib hydrochloride

Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Drug: isotretinoin

Given PO
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret

Other: laboratory biomarker analysis

Correlative study

Genetic: protein expression analysis

Correlative study

Detailed Description:


I. To determine the recommended phase II doses of erlotinib (erlotinib hydrochloride) and 13-cis-retinoic acid (CRA) when administered to adults with recurrent malignant glioma who are not receiving cytochrome P450 enzyme-inducing antiepileptic drugs (EIAEDs).


I. To assess dose-related toxicities. II. To measure 6 month progression-free survival and overall survival. III. To estimate response rates in those patients with measurable disease. IV. To evaluate for epidermal growth factor receptor (EGFR)vIII, phosphatase and tensin homolog (PTEN), cyclin D1, cyclin E, and RARbeta1 expression in tumor samples from enrolled patients as predictors of clinical benefit from this combination.

OUTLINE: This is a dose-escalation study.

Patients receive isotretinoin orally (PO) once daily (QD) on days 1-21 and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for up to 2 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Histologically proven malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) which is progressive or recurrent after radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible Karnofsky performance status of >= 60% Patients – both males and females – with reproductive potential (i.e., premenopausal or menopausal for less than 1 year and not surgically sterilized) must practice at least 2 contraceptive measures throughout the study Patients must be registered and meet all the requirements of iPLEDGE in order to receive 13-cis-Retinoic Acid (CRA) Patients must provide verbal and written informed consent to participate in the study Patients must have a Mini Mental Status Exam score >= 15 Patients must have a 12-lead electrocardiogram (EKG) without evidence of any clinically significant abnormalities Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelets >= 100,000/mm^3 Aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN) (ULN = 50 U/L) Alanine aminotransferase (ALT) =< 2.5 ULN (ULN = 50 U/L) Total Bilirubin =< 1.5 mg/dL Alkaline phosphatase (Alk. Phos) =< 5X ULN (ULN = 125 U/dL) Estimated (Estim.) creatinine (Cr) Clearance > 50 ml/min Fasting total cholesterol < 300 mg/dL Fasting triglycerides < 250 mg/dL Two separate, laboratory pregnancy tests within 14 days of registration (for women of childbearing potential) Patients must have recovered from the toxicity of prior therapy; specifically, there must be at least a 3 month interval from the completion of the most recent course of radiation therapy, at least a 3 month interval from the implantation of Gliadel wafer(s), at least a 3 week interval from the completion of a non-nitrosourea-containing chemotherapy regimen, and at least a 6 week interval from the completion of a nitrosourea-containing chemo-regimen

Exclusion Criteria:

Pregnant or breast-feeding women Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction, severe psychiatric illness that would limit compliance with study requirements, or any other disorder that would be incompatible with the study therapy Any history of inflammatory bowel disease Any history of uncontrolled depression, any history of hospitalization for depression, or any history of suicidal thoughts or attempt(s) Patients receiving concurrent therapy for their tumor (with the exception of steroids) Must have at least a 10 day interval from last dose of vitamin A, tetracyclines, micro-dosed progesterone preparations, norethindrone/ethinyl estradiol, St. John’s Wort, fish oil supplements, or phenytoin or other P450 enzyme inducing antiepileptic drugs Current smokers (Smoking >= 11 cigarettes per day), as smoking increases metabolism and decreases serum levels of erlotinib Participants may not have received prior EGFR inhibitors for any disease Patients with a history of allergic reactions to 13-cis-retinoic acid (CRA) or compounds of similar biologic or chemical composition to CRA Known allergy to proton pump inhibitors

  Contacts and Locations

Please refer to this study by its identifier: NCT01103375

United States, North Carolina
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Glenn J. Lesser     336-716-9527    
Principal Investigator: Glenn J. Lesser            
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Principal Investigator: Glenn Lesser Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University Identifier: NCT01103375    
History of Changes
Other Study ID Numbers: CCCWFU 91209, NCI-2010-00132
Study First Received: April 13, 2010
Last Updated: March 9, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:

Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on August 21, 2012

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