Radiochemotherapy With Panitumumab in the Localised Epidermoid Carcinoma of the Anus

Study Overview
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Brief Summary
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Treatment is based on radiochemotherapy for locally advanced tumours. The objective of treatment is to provide a cure without resorting to abdominoperineal amputation, while preserving sphincter function. The prognosis is mainly related to tumour size and lymph node invasion. The large majority of patients do not show any spread remote from the tumour at the time of diagnosis (2). Recurrences are mainly of a local/regional nature and require abdominoperineal amputation. This type of intervention is not always possible or complete, which then gives rise to the particularly distressing risk of local progression, with survival at 3 years of approximately 30% (3). It is therefore very important to achieve a complete and permanent tumour response from initial treatment with radiochemotherapy. Furthermore, the use of an anti-EGFR antibody in combination with exclusive radiotherapy in ENT cancer was able to increase recurrence-free survival and overall survival in these patients. These data are in favour of the use of a combination of chemotherapy and anti-EGFR antibodies in epidermoid cancer of the anus.

Official Title
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Phase I-II on Radiochemotherapy Combined With Panitumumab in the Treatment of Localised Epidermoid Carcinoma of the Anus

Conditions
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Epidermoid Carcinoma, Anus

Intervention / Treatment
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* Drug: radiochemotherapy
* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven epidermoid carcinoma of the anus Locally advanced tumour without metastases Stage T2>3 cm or T3 or T4, irrespective of N Stage N1-N3 irrespective of T stage (T1 to T4) General condition WHO 0-1 Life expectancy > 3 months Signed informed consent form Age > 18 years Effective contraception in female and/or male patients having reached sexual maturity during treatment and up to 6 months after the end of treatment CD4 > 400 / mm3 Measureable tumor on at least one of the following exams : MRI, endoscopic ultrasonography, clinical exam Exclusion Criteria: Presence of metastases Previous anti-EGFR therapy Stage T1N0 or T2 < 3 cm N0 History of pelvic radiotherapy At least one of the following laboratory test results: Neutrophils < 1500 /mm3, platelets < 100 000 /mm3, Hb < 9 g/dl, leukocytes < 3000/mm3, blood bilirubin > 1.5 times the upper limit of the normal range, transaminase (ASAT and ALAT) > 2.5 times the upper limit of the normal range, creatinine clearance < 50 mL/min (Cockcroft's formula Appendix x), Mg2+ < the lower limit of the normal range, Ca2+ < the lower limit of the normal range Significant coronary artery disease or myocardial infarction in the past year Follow-up not possible due to psychological or geographic reasons History of interstitial pneumonitis or pulmonary fibrosis History of malignant disease in the past five years apart from basocellular skin carcinoma or in situ cervical carcinoma having received adequate treatment Pregnant or breast-feeding women, women of child-bearing potential not having taken a pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 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: 5Fu-mitomycine-panitumumab + radiotherapy<br>5 FU = 400 or 600 or 80 or 1000 mg depending of phase I results, days 1 to 4 weeks 1, 5 and 8 mitomicyne = 10 mg/m² day 1 week 1 and days 1, weeks 5 and 8 Panitumumab = 3 or 6 mg/kg (depending of phase I results) days 1, weeks: 1, 3, 5, 8 and 10 | Drug: radiochemotherapy<br>* Radiotherapy : PTV1 45 Gy 5 weeks PTV2 20 Gy 2 weeks Chemotherapy : 5Fu (400 to 1000 mg/m²) mitomycin : 10 mg/m²<br>Drug: Panitumumab<br>* 3 or 6 mg/kg (according to dose level)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment |  | 8 weeks evaluations after the end of the treatment by radiochemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial response rate, stable disease and progression |  | 6 weeks and 17 weeks after the beginning of treatment | 
| Colostomy-free survival |  | At 3 years after randomization | 
| Recurrence-free survival at 3 years |  | At 3 years after randomization | 
| Overall survival |  | At 3 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anus, carcinoma, panitumumab, mitomycine, 5Fu, radiotherapy