Cetuximab, Chemotherapy, and Radiation Therapy for Operable Stage III or IV Head and Neck Cancer

Summary

RATIONALE: 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. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving cetuximab after surgery may kill any tumor cells that remain.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients who are undergoing surgery for stage III or stage IV head and neck cancer.

Conditions

• Head and Neck Cancer

Interventions

BIOLOGICAL

Cetuximab

Induction: An initial dose of cetuximab (C225) 400 mg/m2 (over 2 hours) was given week 1 only. Then, C225 was administered at dose of 250 mg/m2 (over 1 hour) weekly for 5 weeks. Concurrent Chemoradiation (Weeks 9-13): C225 was administered at 250 mg/m2/wk (over 1 hour). Restaging Biopsy of Primary Site (Week 14): Patients with positive biopsy of the primary site at week 7 or patients without a clinical complete response at the primary site after induction therapy were scheduled for re-biopsy of the primary site at week 14 after concurrent therapy (50 Gy). If the biopsy were negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

DRUG

Carboplatin

Induction Therapy (Week 1-6): The induction chemotherapy starting at week 1 included paclitaxel 90 mg/m2 IV over 1 hour weekly and carboplatin AUC = 2 IV over 30 minutes weekly. The paclitaxel and carboplatin doses were given on the same day, 1 hour after C225 dose was administered. For paclitaxel and carboplatin therapy, rounding of doses (to next decimal if above 0.5 and to lower decimal if below 0.5) was permitted. Concurrent Chemoradiation (Weeks 9-13): Concurrent chemotherapy was consisted of paclitaxel following cetuximab at 30 mg/m2/wk (over 1 hour) and carboplatin following paclitaxel at AUC = 1/week (over 15 minutes). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

DRUG

Paclitaxel

Induction Therapy (Week 1-6): The induction chemotherapy starting at week 1 included paclitaxel 90 mg/m2 IV over 1 hour weekly and carboplatin AUC = 2 IV over 30 minutes weekly. The paclitaxel and carboplatin doses were given on the same day, 1 hour after C225 dose was administered. For paclitaxel and carboplatin therapy, rounding of doses (to next decimal if above 0.5 and to lower decimal if below 0.5) was permitted. Concurrent Chemoradiation (Weeks 9-13): Concurrent chemotherapy was consisted of paclitaxel following cetuximab at 30 mg/m2/wk (over 1 hour) and carboplatin following paclitaxel at AUC = 1/week (over 15 minutes). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

RADIATION

Radiation therapy

Concurrent Chemoradiation (Weeks 9-13): Radiation was given at 200cGy/d/5 weeks for a total dose of 50Gy (5000 cGy). Patients with a negative initial biopsy at week 7 were scheduled to continue concurrent therapy to complete radiation (68-72Gy). If the biopsy was negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy). Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Eastern Cooperative Oncology Group

  lead NETWORK

Principal Investigators

• Harold J. Wanebo, MD · Roger Williams Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-01-06

Primary Completion

2010-02-28

Completion

2011-02-28