Radiochemotherapy With Panitumumab in the Localised Epidermoid Carcinoma of the Anus

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
5Fu-mitomycine-panitumumab + radiotherapy	radiochemotherapy	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
5Fu-mitomycine-panitumumab + radiotherapy	Panitumumab	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

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With Complete Response to Treatment	8 weeks evaluations after the end of the treatment by radiochemotherapy	Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance. The responses were validated by an independent committee: * In the event of a discrepancy between the investigator and the independent committee, the independent committee's response was used; * in case of uncertainty of the investigator on the response, the committee decided on the response in view of the clinical and morphological data; This endpoint was assessed 8 weeks after the end of treatment (week 15). A patient who died (regardless of cause) was considered a failure for the primary endpoint

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With Complete Response to Treatment	16 weeks after the end of the treatement by radiotherapy	Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance according to the investigator's opinion
3 Years Colostomy-free Survival (CFS)	At 3 years after inclusion	It was defined as the time from inclusion to the date of colostomy or death (from any cause). Patients alive without colostomy were censored at date of last news. If a patient had a shunt colostomy and continuity wasrestored, the patient was counted among the patients without a colostomy.
Recurrence-free Survival (RFS) at 3 Years	At 3 years after inclusion	It was defined as the time from inclusion to the date of first recurrence (local, regional, metastatic and second anal cancer) or death. Patients alive without recurrence were censored at date of last news.
Overall Survival (OS) at 12 Months	At 12 months after inclusion	The percentage was evaluated at 12 months using the Kaplan Meier estimation. In the safety part all the death collected during the study will be reported.

Locations (14): Clinique Privée - Plein Ciel
🇫🇷
Mougins, France
Pessac - Hôpital Haut Lévêque
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Bordeaux, France
Centre d'oncologie et de radiothérapie du Parc
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Dijon, France
CH - Hopitaux civils de Colmar
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Colmar, France
CH - CHBS - Hôpital du Scorff
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Lorient, France
Centre Oscar Lambret
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Lille, France
Centre Léon Bérard
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Lyon, France
Institut Régional du Cancer Montpellier
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Montpellier, France
Institut Curie
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Saint Cloud, France
CHU
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Saint Priest en Jarez, France
Cario - HPCA - Hôpital privé des Côtes D'Armor
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Plérin, France
Centre Eugène Marquis
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Rennes, France
CH - Annecy Genevois
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Pringy, France
CAC - Paul Strauss
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Strasbourg, France