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)

Centre Francois Baclesse

Status and phase: Active, not recruiting; Phase 2

Conditions: Locally Advanced Anal Canal Cancer

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02701088

CANAL-IMRT-01

Details and patient eligibility

About

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.

Enrollment: 71 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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71 participants in 1 patient group

Concomitant chemotherapy and radiotherapy

Experimental group

Description:

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

Treatment:

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

Drug: 5Fluorouracile and Mitomycin-C