Clinical Trial: Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer

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

Official Title: A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma

Brief Summary: This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, 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. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1).

II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2).

III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients.

IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients.

SECONDARY OBJECTIVES:

I. Compare, preliminarily, the toxicity and antitumor activity profiles of these regimens in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib and bevacizumab.

Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.

  • Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I) [ Time Frame: 28 days ]
    The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
  • MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II) [ Time Frame: 28 days ]
    The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.


    • Original Primary Outcome:

    Current Secondary Outcome:

    • Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria [ Time Frame: 6 months ]
      The estimated rate and their 95% confidence interval, will be reported.
    • Median time to progression [ Time Frame: Up to 1 month ]
    • Progression-free survival [ Time Frame: From the start of the treatment until the date the criteria for progression are met or the date the patient is taken off study for any reason, assessed up to 1 month ]


    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: January 7, 2005
    Date Started: January 2005
    Date Completion:
    Last Updated: June 10, 2014
    Last Verified: December 2012