Clinical Trial: Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

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

Official Title: A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors

Brief Summary: This phase I trial studies the side effects and best dose of cetuximab when given together with everolimus in treating patients with metastatic or recurrent colon cancer or head and neck cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cetuximab together with everolimus may be an effective treatment for colon cancer or head and neck cancer

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the safety, dose-limiting toxicity and maximum tolerated dose of daily RAD001 (everolimus) when given in combination with a fixed dose of weekly cetuximab in patients with solid tumors.

SECONDARY OBJECTIVES:

I. Determine whether a pharmacokinetic interaction exists between RAD001 and CETUXIMAB in patients treated with this regimen.

II. Determine preliminary clinical evidence of anti-tumor activity by time to progression and Response Evaluation Criteria in Solid Tumors (RECIST) criteria with this regimen.

III. Determine the association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen.

IV. Determine the pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens.

OUTLINE: This is a dose-escalation study of everolimus.

Patients receive everolimus orally (PO) once daily (QD) on days -14 and then 1-28. Patients also receive cetuximab intravenously (IV) over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for at least 1 year.


Sponsor: Fox Chase Cancer Center

Current Primary Outcome: Number of patients with dose limiting toxicity [ Time Frame: Day -14 through Day 28 of Cycle 1 ]

Dose-limiting toxicity defined as any grade 3 or greater non-hematologic, grade 4 thrombocytopenia, grade 4 neutropenia lasting more than 5 days, grade 4 febrile neutropenia requiring hospitalization or treatment delay more than 2 weeks due to unresolved toxicity.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Composite Pharmacokinetic (PK) Analysis [ Time Frame: At days -14, 1,and 22 at 1, 2, 3, 6, and 24 hours after drug treatment and day -7 and prior to dosing on day -4 ]
    PKs derived from serum concentrations versus time for RAD001 on day -14, 1, and 22 at 1, 2, 3, 6, and 24 hours after drug administration as well as day -7 (h 168) and prior to dosing on Day 4.
  • Preliminary clinical evidence of anti-tumor activity by time to progression and RECIST criteria with this regimen [ Time Frame: Baseline and every 2 courses (8 weeks) ]
  • Association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen [ Time Frame: Baseline, 24 hours post-treatment on day 22 ]
  • Pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens [ Time Frame: At baseline, 24 hours post-therapy on day 22 ]


Original Secondary Outcome: Same as current

Information By: Fox Chase Cancer Center

Dates:
Date Received: October 20, 2011
Date Started: November 2008
Date Completion:
Last Updated: July 6, 2012
Last Verified: July 2012