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