Clinical Trial: Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

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

Official Title: A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosi

Brief Summary: This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving sunitinib together with cetuximab and radiation therapy may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety, the maximum tolerated dose, and the dose limiting toxicity of sunitinib malate when administered in combination with cetuximab and radiotherapy in patients with locally advanced, recurrent, or second primary poor prognosis, high-risk squamous cell carcinoma of the head and neck.

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of this regimen. II. To explore the tolerability and feasibility of sunitinib malate when administered in combination with cetuximab and radiotherapy in these patients.

III. To assess the best overall response rate (complete and partial response) after completion of treatment.

IV. To assess the locoregional control rate. V. To assess the distant control rate. VI. To assess the pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

*NOTE: *Patients may have resection prior to enrollment on protocol provided they have high-risk features for recurrence.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic analysis of sunitinib
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Maximum-tolerated dose (MTD) of sunitinib malate [ Time Frame: Up to 7-9 weeks ]

MTD is defined as the dose level immediately below the non-tolerated dose. The study will utilize a standard "3+3" design to determine the MTD. Dose limiting toxicities (DLTs) used for determining escalation of dose will be those occurring within the period of radiotherapy. Toxicity will be summarized by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria.


Original Primary Outcome: Maximum tolerated dose of sunitinib malate

Current Secondary Outcome:

  • Objective tumor response rates [ Time Frame: From the start of the treatment to up to 6 years ]
    Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The efficacy analysis population (an exploratory analysis of those patients on study for the MTD) will consist of all subjects who received at least 1 dose of sunitinib. Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
  • Locoregional control rates [ Time Frame: Up to 6 years ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
  • Disease control rates [ Time Frame: Up to 6 years ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
  • Locoregional recurrence rates [ Time Frame: At 3 years ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
  • Time to progression [ Time Frame: From the date of registration to the date of progressive disease or death from any cause ]
    Time to progression using Kaplan-Meier product limit curves will be calculated.
  • Overall survival time [ Time Frame: From the date of registration to the date of death or date of last patient contact if censored ]
    Overall survival using Kaplan-Meier product limit curves will be calculated.
  • Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube [ Time Frame: Prior to and up to 24 hours after the start of sunitinib malate ]


Original Secondary Outcome:

  • Objective tumor response rates
  • Locoregional control rates
  • Disease control rates
  • Locoregional recurrence rates at years 1, 2, and 3
  • Time to progression
  • Overall survival
  • Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 20, 2009
Date Started: July 2008
Date Completion:
Last Updated: July 1, 2013
Last Verified: July 2013