Trial Information

Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma

OBJECTIVES:

Primary

- Determine whether the addition of cetuximab to combined modality therapy (CMT)
comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by
≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage
I-IIIB invasive anal carcinoma.

Secondary

- Determine objective response rate (complete and partial), progression-free survival,
relapse-free survival, colostomy-free survival, and overall survival.

- Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation
therapy combined with cetuximab.

- Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV)
infection and anal cytology.

- Evaluate whether moderate to strong expression of epidermal growth factor receptor,
PI3K, and P-Akt (as determined by immunohistochemistry) is associated with an increased
risk of local failure.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment arms.

- Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin IV over 60
minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on
days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes
on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and
undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.
Treatment continues in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60
minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over
60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11
and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on
day 8. Treatment continues in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.