Neoadjuvant Cetuximab, Fluorouracil, and Pelvic Irradiation in Treating Patients With Locally Advanced or Locally Recurrent Rectal Cancer

OBJECTIVES:

Primary

- Determine the safety profile of neoadjuvant cetuximab, fluorouracil, and pelvic
irradiation in patients with locally advanced or locally recurrent rectal cancer.

Secondary

- Determine the activity of this regimen, in terms of pathological complete response
rate, in these patients.

OUTLINE: This is a non-randomized, open-label, pilot study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and
64 and fluorouracil IV continuously on days 1-42. Patients undergo whole-pelvic radiotherapy
once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Treatment continues in the
absence of disease progression or unacceptable toxicity.

Approximately 1-3 weeks after completion of study treatment, patients undergo surgical
resection followed by adjuvant chemotherapy off-study.

Patients are followed for up to 5 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed rectal adenocarcinoma meeting 1 of the following staging
criteria:

- Locally advanced disease

- Resectable (uT3) disease

- Primary gross transmural tumor that is not adherent to adjacent pelvic
structures by endorectal ultrasound

- Primary tethered or unresectable (cT4 or uT4) disease

- Primary tumor is contiguous with or adherent or fixed to adjacent
pelvic structures by clinical exam and CT scan

- Primary surgery would likely leave residual tumor

- Small volume extrapelvic metastases allowed

- Recurrent disease after definitive resection

- Disease limited to the pelvis

- Requires combined modality treatment

- Epidermal growth factor receptor status-positive, -negative, or -unknown

- If previously treated with adjuvant fluorouracil-based chemotherapy, no disease
recurrence during or within 12 months after completion of adjuvant therapy

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0 -1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Hemoglobin > 8.0 g/dL

- Platelet count > 150,000/mm^3

Hepatic

- Not specified

Renal

- Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

- No myocardial infarction within the past 6 months

- No evidence of uncontrolled congestive heart failure requiring therapy

Other

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- No known severe hypersensitivity to cetuximab or any of its excipients

- No uncontrolled infection

- No high-grade bowel obstruction (bowel lumen ≤ 1 cm) unless patient has undergone
protective surgical diversion or endoscopic stenting procedure

- No other concurrent medical or psychiatric condition or disease that would preclude
study participation

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 3 months
after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior cetuximab

- No prior murine or chimeric monoclonal antibody therapy

- No prior biological response modifiers for metastatic colorectal cancer

- No concurrent anti-vascular endothelial growth factor/Flk-1 monoclonal antibody
therapy

- No other concurrent antibody therapy or immunotherapy

- No concurrent gene therapy

- No concurrent vaccine therapy

- No concurrent angiogenesis inhibitors, including thalidomide

Chemotherapy

- See Disease Characteristics

- No prior chemotherapy for metastatic colorectal cancer

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy

Radiotherapy

- No prior radiotherapy for metastatic colorectal cancer

- No prior pelvic radiotherapy

- No other concurrent radiotherapy

Surgery

- See Disease Characteristics

- Fully recovered from prior oncologic or other major surgery

Other

- No other prior therapy that targets the epidermal growth factor receptor pathway

- No other concurrent experimental therapy or drugs

- No concurrent matrix metalloprotease inhibitors

- No concurrent participation in another clinical study