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 (CANAL-IMRT-01)

Phase II 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

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Anal Canal Cancer
• Intervention / Treatment: Drug: 5Fluorouracile and Mitomycin-C; Radiation: Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Institut de Cancérologie de l'Ouest - Centre Paul Papin
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Lyon, France
    • Centre Leon Berard
  • Nice, France
    • Centre Antoine Lacassagne
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest
  • Strasbourg, France
    • Centre Paul Strauss
  • Toulouse, France
    • IUCT-Oncopole
  • Vandœuvre-lès-Nancy, France, 54519
    • Institut de cancerologie de Lorraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Concomitant chemotherapy and radiotherapy; 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; 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).; Radiation: Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Measured by the EORTC QLQ-C30 (Version 3.0)	The EORTC QLQ-C30 is a cancer-specific health-related quality of life questionnaire comprising 30 items. It assesses five functional domains (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, pain, and nausea/vomiting), a global health status/quality of life scale, and several single-item symptom measures. Scores are linearly transformed to a 0-100 scale; higher functional and global health scores indicate better functioning/quality of life, whereas higher symptom scores indicate greater symptom burden.	6 months after treatment start
The Acute and Late Toxicities Assessed According to NCI CTCAE v4.03	Acute toxicity is defined as toxicity observed within 3 months after treatment initiation. Late toxicity is defined as toxicity observed 3 months after treatment initiation. Here we described the number of patients who observed acute and late toxicities. Details will be given in adverse events description.	From treatment start to 24 months 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	The EORTC QLQ-CR29 is a colorectal cancer-specific quality of life module designed to complement the QLQ-C30. It assesses disease- and treatment-related symptoms and functional issues, including urinary frequency, blood and mucus in stool, stool frequency, body image, anxiety, sexual function, and other gastrointestinal and treatment-related symptoms. Scores are linearly transformed to a 0-100 scale; higher functional scores indicate better functioning, whereas higher symptom scores indicate greater symptom burden.	6 months after treatment start
Quality of Life Measured by the Vaizey Incontinence Scale	Vaizey Score (St. Mark's Incontinence Score): a validated instrument used to assess anal sphincter function and the severity of fecal incontinence. The scale evaluates the frequency of incontinence to gas, liquid, and solid stool, the need to wear pads, use of constipating medication, and lifestyle alterations. Scores range from 0 to 24, with higher scores indicating worse continence and greater impairment of sphincter function.	6 months after treatment start
The Acute Toxicities Assessed According the SOMA/LENT Scale	The Subjective SOMA/LENT (Late Effects on Normal Tissues - Subjective, Objective, Management, and Analytic) scale assesses patient-reported late radiation toxicity across multiple symptom domains. Each symptom item (e.g., stool frequency, urinary frequency, vaginal dryness, dyspareunia) is scored separately on a 5-point ordinal scale ranging from 0 to 4, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms, and 4 = very severe or disabling symptoms. Higher scores indicate worse late radiation-related toxicity. No overall total score was calculated; each symptom domain is reported separately.	At 3 months after treatment initiation

Collaborators and Investigators

• Sponsor: Centre Francois Baclesse
• Collaborators: Accuray Incorporated
• Investigators: Principal Investigator: Carmen FLORESCU, MD, Centre Francois Baclesse

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): June 25, 2021
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: December 23, 2015
• First Submitted That Met QC Criteria: March 2, 2016
• First Posted (Estimated): March 8, 2016

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Quinones; Azirines; Mitomycins; Indolequinones; Mitomycin
• Other Study ID Numbers: CANAL-IMRT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO