Clinical Trial: Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I Single Arm Open Label Study of Erlotinib and 13-cis-Retinoic Acid (CRA) in Patients With Recurrent Malignant Gliomas

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

Detailed Summary:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.


Sponsor: Wake Forest University Health Sciences

Current Primary Outcome: Recommended phase II doses of erlotinib hydrochloride and isotretinoin [ Time Frame: 3 weeks ]

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.


Original Primary Outcome: Recommended phase II doses of erlotinib hydrochloride and isotretinoin

Current Secondary Outcome:

  • Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 2 years ]
  • Progression-free survival [ Time Frame: At 6 months ]
  • Overall survival [ Time Frame: At 6 months ]
  • Response rates (complete or partial response) [ Time Frame: Up to 2 years ]
  • EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples [ Time Frame: Pre-study ]


Original Secondary Outcome:

  • Toxicity as assessed by NCI CTCAE v3.0
  • Progression-free survival [ Time Frame: At 6 months ]
  • Overall survival
  • Response rates
  • EGFRvIII, PTEN, cyclin D1, cyclin E, and RARbeta1 expression in tumor samples


Information By: Wake Forest University Health Sciences

Dates:
Date Received: April 13, 2010
Date Started: May 2010
Date Completion:
Last Updated: February 20, 2017
Last Verified: February 2017