Clinical trial NCT02701088: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Anal Canal Cancer
Lead sponsor: Centre Francois Baclesse
Sponsor class: OTHER
Collaborators: name: Accuray Incorporated
First posted: 2016-03-08
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Efficacy: The 3-month locoregional control rate
timeFrame: 3 months after the end of radiotherapy
measure: Tolerance profile: Proportion of patients with no significant toxicities responsible for irradiation breaks
timeFrame: Until 11 weeks after treatment start
Secondary outcomes:
measure: Quality of life measured by the EORTC QLQ-C30 (version 3.0)
timeFrame: From treatment start to 5 years after the end of radiotherapy
measure: The acute and late toxicities assessed according to NCI CTCAE v4.03
timeFrame: From treatment start to 5 years after the end of radiotherapy
measure: 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
timeFrame: at 6 and 12 months after the end of radiotherapy
measure: Duration of response defined by the time elapsed from first objective response to progression or death from any cause
timeFrame: From months 3 to progression
measure: Quality of life measured by the additional colorectal module QLQ-CR 29
timeFrame: From treatment start to 5 years after the end of radiotherapy
measure: Quality of life measured by the Vaizey incontinence scale
timeFrame: From treatment start to 5 years after the end of radiotherapy
measure: The acute and late toxicities assessed according the SOMA/LENT scale
timeFrame: From treatment start to 5 years after the end of radiotherapy
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest - Centre Paul Papin
city: Caen
country: France
facility: Centre François Baclesse
city: Lyon
country: France
facility: Centre Léon Berard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: St HERBLAIN
country: France
facility: Institut de cancérologie de l'Ouest
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: IUCT-Oncopole
city: Vandoeuvre-les-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
Study officials:
affiliation: Centre François Baclesse
name: Carmen FLORESCU, MD
role: PRINCIPAL_INVESTIGATOR
References: