Study of SIB-IMRT in Combination With 5-FU and Mitomycin-C Among Patients With Locally Advanced Anal Canal Cancer: Efficacy, Safety and Quality of Life

NCT02701088 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CANAL-IMRT-01
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 8

Brief Summary

Anal canal carcinoma (ACC) represents 1.2% of digestive cancers. Its incidence is increasing. As epidermoid ACC (95% of ACC) are particularly sensitive to radio and chemotherapy, concomitant radio-chemotherapy is the standard treatment of locally advanced ACC, with proven efficacy on locoregional control, anal sphincter preservation, progression-free survival and complete response rate higher than 80%. Nevertheless, conventional radiotherapy frequently induces significant non-haematological toxicities requiring treatment interruptions. Thus, treatment usually includes a chemotherapy (5-Fluorouracil and Mitomycine-C) and 25 fractions of 1.8 Gy followed by a planned 1-week (or more) interruption and a boost, for a total 54-60 Gy radiation dose over 9 weeks. Considering the numerous anatomic pelvic structures, ACC has become a localisation of interest for Intensity-Modulated Radiation Therapy (IMRT) associated with less toxicity. However, IMRT induces grade≥3 cutaneous toxicities requiring irradiation breaks. Dose escalade did not show its interest: 60 Grays remains the standard. Assuming the deleterious effect of increased overall treatment time on local control and survival in head-and-neck and cervical cancers and the epidermoid histology of ACC, the benefit of no irradiation break on ACC tumour control is of interest. IMRT offers the possibility to deliver different doses to different target volumes simultaneously by altered fractionation schedule like SIB-IMRT (simultaneously integrated boost-IMRT). Several SIB-IMRT schedules have been retrospectively evaluated. Similar results were observed with moderate doses and schedules delivering higher doses with short interruptions. Nevertheless, standard SIB-IMRT schedule in ACC still not exist.

Conditions

Locally Advanced Anal Canal Cancer

Outcome Measures

Primary Outcomes (2)

• Efficacy: The 3-month locoregional control rate

  The 3-month locoregional control rate after the end of IMRT by helical tomotherapy defined by the proportion of patients alive with no local disease progression 3 months after the end of radiotherapy

  3 months after the end of radiotherapy

• Tolerance profile: Proportion of patients with no significant toxicities responsible for irradiation breaks

  Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks

  Until 11 weeks after treatment start

Secondary Outcomes (7)

• Quality of life measured by the EORTC QLQ-C30 (version 3.0)

  From treatment start to 5 years after the end of radiotherapy

• The acute and late toxicities assessed according to NCI CTCAE v4.03

  From treatment start to 5 years after the end of radiotherapy

• The 6- and 12-month locoregional control rates defined by the proportion of patients with no local disease progression at 6 and 12 months after the end of radiotherapy

  at 6 and 12 months after the end of radiotherapy

• Duration of response defined by the time elapsed from first objective response to progression or death from any cause

  From months 3 to progression

• Quality of life measured by the additional colorectal module QLQ-CR 29

  From treatment start to 5 years after the end of radiotherapy

Study Arms (1)

Concomitant chemotherapy and radiotherapy

EXPERIMENTAL

Chemoradiotherapy with two cycles of 5FU and Mitomycin-C plus radiotherapy by SIB-IMRT (for simultaneous integrated boost intensity modulated radiation therapy) day 1 to day 50 in 36 fractions

Drug: 5Fluorouracile and Mitomycin-C; Radiation: Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy

Interventions

5Fluorouracile and Mitomycin-C DRUG

All the patients will receive radiochemotherapy with two cycles of 5FU (1,000 mg/m²/d with 96-h infusion, days 1-5 and 29-33 of SIB-IMRT) and Mitomycin-C (10 mg/m², days 1 and 29).

Concomitant chemotherapy and radiotherapy

Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy RADIATION

SIB-IMRT schedule of 61.2 Gy/1.7 Gy to the primary tumor, 57.60 Gy / 1.6 Gy to involved nodes, and 54 / 1.5 Gy to elective pelvic lymph nodes.

Concomitant chemotherapy and radiotherapy

Eligibility Criteria

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

You may qualify if:

• WHO performance status ≤ 2
• Age \> 18 years
• Epidermoid anal canal carcinoma histologically proven, locally advanced with an indication of radiation of pelvic and inguinal nodes concomitantly to chemotherapy
• The T corresponds to the larger dimension of tumor at the rectal examination and the N is assessed by imaging pelvic MRI-imaging, CT-scan, optionally PET-CT). Eligible tumors are: T2 more than 4 cm N0-N3, T2-T4 N1-N3 or usN1, T3-T4 N0, M0 according to the 6th edition of the American Joint Committee on cancer staging manual.
• Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow, hepatic and renal function defined as follows: hemoglobinemia, neutrophil, platelet counts, bilirubin and creatinin level
• Informed consent form

You may not qualify if:

• Previous invasive cancer within 5 years except basocellular cancer and in situ cervical cancer
• Tumors with predominant skin involvement
• Presence of metastases
• History of pelvic irradiation
• Contraindication to radiotherapy or chemotherapy
• Known HIV positive patients

Sponsors & Collaborators

• Centre Francois Baclesse: lead
• Accuray Incorporated: collaborator

Study Sites (8)

Institut de Cancérologie de l'Ouest - Centre Paul Papin

Angers, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Léon Berard

Lyon, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut de cancérologie de l'Ouest

Saint-Herblain, 44805, France

Location

Centre Paul Strauss

Strasbourg, France

Location

IUCT-Oncopole

Toulouse, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

MeSH Terms

Interventions

Mitomycin

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Carmen FLORESCU, MD

  Centre François Baclesse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: March 8, 2016
• Study Start: December 1, 2015
• Primary Completion: June 25, 2021
• Study Completion: December 1, 2025
• Last Updated: September 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)