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

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy such as fluorouracil work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with fluorouracil and radiation therapy may kill more tumor cells.

Detailed Description
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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.

Official Title
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A Pilot Clinical Trial of Preoperative Cetuximab With Concurrent Continuous Infusion Fluorouracil and Pelvic Radiation in Patients With Local-Regionally Advanced Rectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: fluorouracil
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab, Fluorouracil, and Pelvic Irradiation<br>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. | Biological: cetuximab<br> <br> Drug: fluorouracil<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activity in terms of pathological complete response rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent rectal cancer, stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum