Locally Advanced Anal Canal Cancer
Conditions
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.
Interventions
DRUG5Fluorouracile 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).
RADIATIONSimultaneously 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.
Sponsors
Centre Francois Baclesse
Accuray Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: The 3-month Locoregional Control Rate | 3 months after the end of radiotherapy | 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 | Until 11 weeks after treatment start | Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Measured by the EORTC QLQ-C30 (Version 3.0) | 6 months after treatment start | 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. |
| The Acute and Late Toxicities Assessed According to NCI CTCAE v4.03 | From treatment start to 24 months after the end of radiotherapy | 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. |
| 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 | 6 months after treatment start | 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. |
| Quality of Life Measured by the Vaizey Incontinence Scale | 6 months after treatment start | 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. |
| The Acute Toxicities Assessed According the SOMA/LENT Scale | At 3 months after treatment initiation | 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. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORCarmen FLORESCU, MD
Centre François Baclesse
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 9 |
| Histology Moderately differentiated transitional carcinoma | 20 Participants |
| Histology No further information available | 12 Participants |
| Histology Poorly differentiated basaloid carcinoma | 22 Participants |
| Histology Well differentiated | 16 Participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 70 |
| other Total, other adverse events | 70 / 70 |
| serious Total, serious adverse events | 26 / 70 |
Outcome results
None listed