Radiation Therapy, Cisplatin, Fluorouracil, and Cetuximab in Treating Patients With Locally Advanced Anal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy together with combination chemotherapy and cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying giving radiation therapy together with cisplatin, fluorouracil, and cetuximab to see how well it works in treating patients with locally advanced anal cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Evaluate the objective response (complete and partial) 8 weeks after completion of study treatment comprising radiotherapy, chemotherapy (fluorouracil and cisplatin), and cetuximab followed by additional radiotherapy in patients with locally advanced anal cancer. Secondary Evaluate colostomy-free survival. Evaluate the local control rate (objective response and stabilization) at 8 weeks. Evaluate relapse-free survival at 5 years. Evaluate the intermediate objective response at the end of week 5 of radiotherapy. Evaluate overall survival at 5 years. Evaluate the duration of response. Evaluate acute toxicities according to CTCAE v3.0. Evaluate late toxicities at 5 years according to CTCAE v3.0. Study the tumor markers associated with response (survival without relapse) and toxicity. Study the genotypes of Fc-receptor immunoglobulins (FCGR2A and FCGR3) and their association with skin toxicity, objective survival, and relapse-free survival. OUTLINE: This is a multicenter study. Patients receive cetuximab IV on days 0, 7, 14, 21, 28, and 35; fluorouracil IV on days 7-10 and 35-38; and cisplatin IV over 2 hours on days 7 and 35. Beginning on day 7, patients also undergo radiotherapy 5 days a week for 5 weeks (weeks 2-6). Two weeks after finishing this treatment, patients undergo additional radiotherapy* 5 days a week for 2 weeks (weeks 9 and 10). NOTE: *Some patients may undergo brachytherapy. Blood and tissue samples are collected for further analysis. After completion of study treatment, patients are followed up for 4 years.

Official Title
-----------------
Phase II Nonrandomized Multicenter Study of the Impact of Radiochemotherapy (65 Gy + Cisplatin + 5FU) Combined With Cetuximab in Patients Presenting With Locally Advanced Anal Cancer

Conditions
-----------------
Anal Cancer

Intervention / Treatment
-----------------
* Biological: cetuximab
* Drug: cisplatin
* Drug: fluorouracil
* Other: laboratory biomarker analysis
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed anal cancer Squamous cell disease Locally advanced, non-metastatic disease One of the following clinical TNM stages: T2, N0, M0 (largest diameter ≥ 3 cm) T3-T4, N0, M0 Any T, N1-N3, M0 No undifferentiated small cell carcinoma or adenocarcinoma Measurable disease according to RECIST criteria Undergone endorectal ultrasound or MRI to evaluate the primary tumor Undergone thoraco-abdomino-pelvic scan to evaluate tumor extension Disease suitable to receive radiotherapy and chemotherapy PATIENT CHARACTERISTICS: ECOG performance status 0-1 Leukocytes ≥ 4,000/mm^3 ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Creatinine clearance > 60 mL/min ALT and AST ≤ 5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Total bilirubin ≤ 1.5 times ULN Not pregnant or nursing Negative pregnancy test No history of cancer within the past 8 years except for in situ cervical cancer or previously treated basal cell carcinoma of the skin No contraindications to any component of study therapy No serious uncontrolled illness No symptomatic grade 1 angina pectoris or angina pectoris ≥ grade 2 No congestive heart failure No peripheral sensory neuropathy No uncontrolled diabetes No HIV positivity No geographical, social, or psychological situations that preclude medical follow up Affiliated with a social security system No patient deprived of liberty or under trusteeship PRIOR CONCURRENT THERAPY: Patients with a diverting colostomy are eligible No prior excision of this tumor No prior chemotherapy or radiotherapy for the treatment of this cancer or any other history of radiotherapy or pelvic brachytherapy No concurrent coumarin anticoagulants, phenytoin, sorivudine or brivudine, antacids, or allopurinol Not registered in another clinical trial with an experimental drug

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: cisplatin|nan|
|Drug: fluorouracil|nan|
|Other: laboratory biomarker analysis|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (complete and partial) according to RECIST criteria at 8 weeks after completion of study treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate at 3 and 5 years |  |  | 
| Colostomy-free survival at 3 and 5 years |  |  | 
| Duration of objective response |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, squamous cell carcinoma of the anus