Trial Information

A Phase I Trial of Tailored Radiation Therapy With Concomitant Cetuximab (C225, NSC #714692) and Cisplatin (NSC #119875) in the Treatment of Patients With Cervical Cancer

OBJECTIVES:

Primary

- Determine the maximum tolerated dose or safe biologically effective dose of cetuximab
when administered in combination with cisplatin, external beam radiotherapy, and
brachytherapy in patients with stage IB-IVA cervical cancer.

- Determine the feasibility of this regimen, in terms of chronic and acute toxic effects,
in these patients.

Secondary

- Determine the distribution of progression-free survival and overall survival of
patients treated with this regimen at 1 year after study entry.

- Determine the site of recurrence (locoregional vs distant) in patients treated with
this regimen up to 1 year after study entry.

- Correlate response or progression-free survival with epidermal growth factor receptor
expression in tumor samples from patients treated with this regimen at 1 year after
study entry.

- Correlate response or progression-free survival with grade of cetuximab-induced rash in
patients treated with this regimen at 1 year after study entry.

OUTLINE: This is a multicenter, dose-escalation study of cetuximab. Patients are stratified
according to nodal status (positive para-aortic and/or pelvic lymph nodes vs negative
para-aortic and pelvic lymph nodes).

Patients receive cetuximab IV over 1-2 hours and cisplatin IV on days 1, 8, 15, 22, 29, and
36 (weeks 1-6). Patients also undergo external beam radiotherapy to the para-aortic and
pelvic lymph nodes OR whole pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33
(weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy
in weeks 6-8 OR 5 applications of high-dose rate (HDR)* brachytherapy once weekly in weeks
4-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: *No external beam radiotherapy is administered on the day of HDR brachytherapy. If the
majority of external beam radiotherapy has been administered, HDR brachytherapy may be
administered in 2 applications per week (separated by at least 72 hours) in order to
complete all treatment within 8 weeks.

Cohorts of 3-6 patients per stratum receive escalating doses of cetuximab 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.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: Approximately 30-100 patients will be accrued for this study.