Radiochemotherapy With Panitumumab in the Localised Epidermoid Carcinoma of the Anus

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2012 by Federation Francophone de Cancerologie Digestive
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT01581840
First received: April 6, 2012
Last updated: August 30, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Epidermoid Carcinoma
Anus
Drug: radiochemotherapy
Drug: Panitumumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Phase I = determination the maximum tolerated dose 5FU and panitumumab in combination with radiotherapy and mitomycin, and thereby to deduce the maximum tolerated dose in patient with localised epidermoid carcinoma of the anus [ Time Frame: 9 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
    Phase I = determine the dose limiting toxicity of 5FU and panitumumab in combination with radiotherapy and mitomycin, and thereby to deduce the maximum tolerated dose in patient with localised epidermoid carcinoma of the anus

  • Phase II = Complete response of the tumor rectal examination and morphological exams [ Time Frame: 8 weeks evaluations after the end of the treatment by radiochemotherapy ] [ Designated as safety issue: No ]
    phase II = Response criteria: complete desappearance of the tumor upon rectal examination and morphological exams (MRI, endoscopic ultrasonography) and non appearance of secondary lesions, response validated by an independant committee.


Secondary Outcome Measures:
  • Phase II = Partial response rate, stable disease and progression [ Time Frame: 6 weeks and 17 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
    • Intermediate objective response rate (complete and partial) at 6 weeks (before the additional radiotherapy). The 80% reduction rate in the largest tumour diameter will also be recorded.
    • Partial response rate, stable disease and progression 8 weeks after the end of treatment

  • Phase II = Colostomy-free survival [ Time Frame: At 3 years after randomization ] [ Designated as safety issue: No ]
  • Phase II = Recurrence-free survival at 3 years [ Time Frame: At 3 years after randomization ] [ Designated as safety issue: No ]
  • Phase II = Overall survival [ Time Frame: At 3 years after randomization ] [ Designated as safety issue: No ]
  • Phase II = Quality of life (EORTC QLQ-C30 + Wexner questionnaire) [ Time Frame: At 3 years after randomization ] [ Designated as safety issue: No ]
    -


Estimated Enrollment: 45
Study Start Date: June 2012
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01581840

Contacts
Contact: MOREAU Marie +33 3 80 39 34 04 marie.moreau@u-bourgogne.fr

Locations
France
Fédération Francophone de Cancérologie Digestive Recruiting
Dijon, Bourgogne, France, 21000
Contact: MOREAU Marie    +33 3 80 39 34 04    marie.moreau@u-bourgogne.fr   
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Principal Investigator: APARICIO Thomas, MD - PhD CHU Avicenne - Bobigny - APHP
  More Information

No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT01581840     History of Changes
Other Study ID Numbers: FFCD 0904
Study First Received: April 6, 2012
Last Updated: August 30, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes

Keywords provided by Federation Francophone de Cancerologie Digestive:
anus
carcinoma
panitumumab
mitomycine
5Fu
radiotherapy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014