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)
Primary Purpose
Locally Advanced Anal Canal Cancer
Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
5Fluorouracile and Mitomycin-C
Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Anal Canal Cancer
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
Sites / Locations
- Institut de Cancérologie de l'Ouest - Centre Paul Papin
- Centre François Baclesse
- Centre Léon Berard
- Centre Antoine Lacassagne
- Institut de cancérologie de l'Ouest
- Centre Paul Strauss
- IUCT-Oncopole
- Institut de Cancérologie de Lorraine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Concomitant chemotherapy and radiotherapy
Arm 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
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Quality of life measured by the EORTC QLQ-C30 (version 3.0)
The acute and late toxicities assessed according to NCI CTCAE v4.03
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
Duration of response defined by the time elapsed from first objective response to progression or death from any cause
Quality of life measured by the additional colorectal module QLQ-CR 29
Quality of life measured by the Vaizey incontinence scale
The acute and late toxicities assessed according the SOMA/LENT scale
Full Information
NCT ID
NCT02701088
First Posted
December 23, 2015
Last Updated
December 7, 2022
Sponsor
Centre Francois Baclesse
Collaborators
Accuray Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02701088
Brief Title
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
Acronym
CANAL-IMRT-01
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
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2015 (Actual)
Primary Completion Date
June 25, 2021 (Actual)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Francois Baclesse
Collaborators
Accuray Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Anal Canal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Concomitant chemotherapy and radiotherapy
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
5Fluorouracile and Mitomycin-C
Intervention Description
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
Radiation
Intervention Name(s)
Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Efficacy: The 3-month locoregional control rate
Description
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
Time Frame
3 months after the end of radiotherapy
Title
Tolerance profile: Proportion of patients with no significant toxicities responsible for irradiation breaks
Description
Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks
Time Frame
Until 11 weeks after treatment start
Secondary Outcome Measure Information:
Title
Quality of life measured by the EORTC QLQ-C30 (version 3.0)
Time Frame
From treatment start to 5 years after the end of radiotherapy
Title
The acute and late toxicities assessed according to NCI CTCAE v4.03
Time Frame
From treatment start to 5 years after the end of radiotherapy
Title
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
Time Frame
at 6 and 12 months after the end of radiotherapy
Title
Duration of response defined by the time elapsed from first objective response to progression or death from any cause
Time Frame
From months 3 to progression
Title
Quality of life measured by the additional colorectal module QLQ-CR 29
Time Frame
From treatment start to 5 years after the end of radiotherapy
Title
Quality of life measured by the Vaizey incontinence scale
Time Frame
From treatment start to 5 years after the end of radiotherapy
Title
The acute and late toxicities assessed according the SOMA/LENT scale
Time Frame
From treatment start to 5 years after the end of radiotherapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carmen FLORESCU, MD
Organizational Affiliation
Centre François Baclesse
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de Cancérologie de l'Ouest - Centre Paul Papin
City
Angers
Country
France
Facility Name
Centre François Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Léon Berard
City
Lyon
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
Institut de cancérologie de l'Ouest
City
St HERBLAIN
ZIP/Postal Code
44805
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
Country
France
Facility Name
IUCT-Oncopole
City
Toulouse
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Vandoeuvre-les-Nancy
ZIP/Postal Code
54519
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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