Radiochemotherapy With Panitumumab in the Localised Epidermoid Carcinoma of the Anus

Sponsor

Federation Francophone de Cancerologie Digestive (Other)

Overall Status

Completed

CT.gov ID

NCT01581840

Collaborator

(none)

Enrollment

Locations

Arm

104

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epidermoid Carcinoma Anus	Drug: radiochemotherapy Drug: Panitumumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Sep 1, 2018

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5Fu-mitomycine-panitumumab + radiotherapy 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 Radiotherapy : PTV1 45 Gy 5 weeks PTV2 20 Gy 2 weeks Chemotherapy : 5Fu (400 to 1000 mg/m²) mitomycin : 10 mg/m² Drug: Panitumumab 3 or 6 mg/kg (according to dose level)

Arm

Intervention/Treatment

Experimental: 5Fu-mitomycine-panitumumab + radiotherapy

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

Radiotherapy : PTV1 45 Gy 5 weeks PTV2 20 Gy 2 weeks Chemotherapy : 5Fu (400 to 1000 mg/m²) mitomycin : 10 mg/m²

Drug: Panitumumab

3 or 6 mg/kg (according to dose level)

Outcome Measures

Primary Outcome Measures

Response to treatment [8 weeks evaluations after the end of the treatment by radiochemotherapy]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Pessac - Hôpital Haut Lévêque	Bordeaux	France
2	CH - Hopitaux civils de Colmar	Colmar	France
3	Centre d'oncologie et de radiothérapie du Parc	Dijon	France
4	Centre Oscar Lambret	Lille	France
5	CH - CHBS - Hôpital du Scorff	Lorient	France
6	Centre Léon Bérard	Lyon	France
7	Institut Régional du Cancer Montpellier	Montpellier	France
8	Clinique Privée - Plein Ciel	Mougins	France
9	Institut Curie	Paris	France
10	Cario - HPCA - Hôpital privé des Côtes D'Armor	Plérin	France
11	CH - Annecy Genevois	Pringy	France
12	Centre Eugène Marquis	Rennes	France
13	Institut Curie	Saint Cloud	France
14	CHU	Saint Priest en Jarez	France
15	CAC - Paul Strauss	Strasbourg	France