Radiochemotherapy With Panitumumab in the Localised Epidermoid Carcinoma of the Anus

NCT01581840 | Completed Phase 1 Results DMC

• 1 other identifier: FFCD 0904
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 15

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.

Conditions

Epidermoid Carcinoma; Anus

Keywords

anus; carcinoma; panitumumab; mitomycine; 5Fu; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Complete Response to Treatment

  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

  8 weeks evaluations after the end of the treatment by radiochemotherapy

Secondary Outcomes (4)

• Percentage of Patients With Complete Response to Treatment

  16 weeks after the end of the treatement by radiotherapy

• 3 Years Colostomy-free Survival (CFS)

  At 3 years after inclusion

• Recurrence-free Survival (RFS) at 3 Years

  At 3 years after inclusion

• Overall Survival (OS) at 12 Months

  At 12 months after inclusion

Study Arms (1)

5Fu-mitomycine-panitumumab + radiotherapy

EXPERIMENTAL

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; Drug: Panitumumab

Interventions

radiochemotherapy DRUG

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

5Fu-mitomycine-panitumumab + radiotherapy

Panitumumab DRUG

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

5Fu-mitomycine-panitumumab + radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead

Study Sites (15)

Pessac - Hôpital Haut Lévêque

Bordeaux, France

Location

CH - Hopitaux civils de Colmar

Colmar, France

Location

Centre d'oncologie et de radiothérapie du Parc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

CH - CHBS - Hôpital du Scorff

Lorient, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Régional du Cancer Montpellier

Montpellier, France

Location

Clinique Privée - Plein Ciel

Mougins, France

Location

Institut Curie

Paris, France

Location

Cario - HPCA - Hôpital privé des Côtes D'Armor

Plérin, France

Location

CH - Annecy Genevois

Pringy, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institut Curie

Saint-Cloud, France

Location

CHU

Saint-Priest-en-Jarez, France

Location

CAC - Paul Strauss

Strasbourg, France

Location

Related Publications (2)

• Vendrely V, Lemanski C, Gnep K, Barbier E, Hajbi FE, Lledo G, Dahan L, Terrebonne E, Manfredi S, Mirabel X, Mammar V, Cowen D, Lepage C, Aparicio T; for FFCD investigators/Collaborators. Anti-epidermal growth factor receptor therapy in combination with chemoradiotherapy for the treatment of locally advanced anal canal carcinoma: Results of a phase I dose-escalation study with panitumumab (FFCD 0904). Radiother Oncol. 2019 Nov;140:84-89. doi: 10.1016/j.radonc.2019.05.018. Epub 2019 Jun 8.

  PMID: 31185328 RESULT

• Vendrely V, Ronchin P, Minsat M, Le Malicot K, Lemanski C, Mirabel X, Etienne PL, Lievre A, Darut-Jouve A, de la Fouchardiere C, Giraud N, Breysacher G, Argo-Leignel D, Thimonnier E, Magne N, Abdelghani MB, Lepage C, Aparicio T; for FFCD investigators/Collaborators. Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial. Radiother Oncol. 2023 Sep;186:109742. doi: 10.1016/j.radonc.2023.109742. Epub 2023 Jun 12.

  PMID: 37315583 DERIVED

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Carcinoma

Interventions

Chemoradiotherapy; Panitumumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Karine Le Malicot
• Organization: Fédération Francophone de Cancérologie Digestive

karine.le-malicot@u-bourgogne.fr

+33 3 80 39 34 79

Study Officials

• Véronique VENDRELY, MD

  Hôpital Haut-Lévêque - Bordeaux

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2012
• First Posted: April 20, 2012
• Study Start: January 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: February 1, 2021
• Last Updated: July 1, 2024
• Results First Posted: July 1, 2024

Record last verified: 2024-06

Locations

FR (15)