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

NCT ID: NCT02701088

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2025-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

5Fluorouracile and Mitomycin-C

Intervention Type: 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).

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

Intervention Type: 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.

Interventions

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).

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Accuray Incorporated

INDUSTRY

Sponsor Role: collaborator

Centre Francois Baclesse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carmen FLORESCU, MD

Role: PRINCIPAL_INVESTIGATOR

Centre François Baclesse

Locations

Institut de Cancérologie de l'Ouest - Centre Paul Papin

Angers, , France

Centre François Baclesse

Caen, , France

Centre Léon Berard

Lyon, , France

Centre Antoine Lacassagne

Nice, , France

Institut de cancérologie de l'Ouest

Saint-Herblain, , France

Centre Paul Strauss

Strasbourg, , France

IUCT-Oncopole

Toulouse, , France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

CANAL-IMRT-01

Identifier Type: -

Identifier Source: org_study_id