Clinical Trial: Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer

Brief Summary: This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with cetuximab and to see how well they work in treating patients with advanced gastrointestinal cancer, head and neck cancer, non-small cell lung cancer, or colorectal cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib hydrochloride and cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib hydrochloride together with cetuximab may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To identify the maximum tolerated dose (MTD). II. To identify the recommended dose (RD) for phase II of erlotinib (erlotinib hydrochloride) in combination with cetuximab in patients (pts) with incurable gastrointestinal, head and neck, or non-small cell lung cancers that are Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type.

SECONDARY OBJECTIVES:

I. To identify dose-limiting toxicities (DLT). II. To perform skin and tumor biopsies to analyze molecular inhibition of the epidermal growth factor receptor (EGFR) signaling pathway, defined as a >= 75% inhibition of phosphorylation of the epidermal growth factor (EGF) receptor or of its downstream effectors tumor protein (p)44/42 mitogen-activated protein kinase (MAPK) or protein kinase B (Akt) or as a >= 25% decrease of marker of proliferation Ki-67 (Ki67) from baseline in either skin or tumor tissue in the majority of patients.

III. To identify the optimal biological dose (OBD). IV. To describe any antitumor effect observed.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride.

Patients receive cetuximab intravenously (IV) over 1-2 hours on days 1, 8, and 15 and erlotinib hydrochloride orally (PO) once daily (QD) on days 8-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Incidence of DLT, defined as recurring grade 2 or greater non-hematological or grade 3 or greater hematological toxicities or skin rash graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE-v3) [ Time Frame: 21 days ]
  • MTD defined as the dose level at which fewer than 2 out of 6 patients experience DLT graded using CTCAE-v3 [ Time Frame: 21 days ]


Original Primary Outcome:

  • Dose-limiting toxicity (phase I)
  • Maximum tolerated dose and recommended phase II dose (phase I)
  • Response rate (phase II)


Current Secondary Outcome:

  • Change in molecular inhibition of the EGFR signaling pathway [ Time Frame: Baseline to up to 4 weeks ]
    These data will be descriptive in nature, with no hypothesis testing. Summary statistics including numbers of subjects that met response criteria, and mean, median and standard deviation in the percent staining, all by dose level.
  • OBD defined as the dose at which either a >= 75% inhibition of phosphorylation of the EGF receptor or of its downstream effectors p44/42 MAPK or Akt is observed, or Ki67 is decreased by >= 25% [ Time Frame: Up to 4 weeks ]
    These data will be descriptive in nature, with no hypothesis testing. Summary statistics including numbers of subjects that met response criteria, and mean, median and standard deviation in the percent staining, all by dose level.
  • Antitumor effect observed [ Time Frame: Up to 4 weeks ]


Original Secondary Outcome:

  • Optimal biological dose (phase I)
  • Antitumor effect (phase I)
  • Progression-free survival at 4 months (phase II)
  • Time to tumor progression (phase II)
  • Median survival (phase II)
  • Safety and tolerability (phase II)


Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 8, 2006
Date Started: January 2007
Date Completion:
Last Updated: September 28, 2015
Last Verified: February 2014