Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

NCT01103375 | Terminated Phase 1 FDA Drug

• 3 other identifiers: IRB00012306NCI-2010-00132CCCWFU 91209
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Recommended phase II doses of erlotinib hydrochloride and isotretinoin

  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.

  3 weeks

Secondary Outcomes (5)

• Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

  Up to 2 years

• Progression-free survival

  At 6 months

• Overall survival

  At 6 months

• Response rates (complete or partial response)

  Up to 2 years

• EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples

  Pre-study

Study Arms (1)

Treatment (enzyme inhibitor, immunotherapy)

EXPERIMENTAL

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

Drug: erlotinib hydrochloride; Drug: isotretinoin; Other: laboratory biomarker analysis; Genetic: protein expression analysis

Interventions

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Treatment (enzyme inhibitor, immunotherapy)

isotretinoin DRUG

Given PO

Also known as: 13-CRA, Amnesteem, Cistane, Claravis, Sotret

Treatment (enzyme inhibitor, immunotherapy)

laboratory biomarker analysis OTHER

Correlative study

Treatment (enzyme inhibitor, immunotherapy)

protein expression analysis GENETIC

Correlative study

Treatment (enzyme inhibitor, immunotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Erlotinib Hydrochloride; Isotretinoin

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Glenn Lesser

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: April 14, 2010
• Study Start: May 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2013
• Last Updated: August 1, 2018

Record last verified: 2018-07

Locations

US (1)