Anus Diseases, Anus Neoplasms, Carcinoma, Carcinoma, Squamous Cell, Neoplasms, Neoplasms, Squamous Cell
Conditions
Keywords
anal cancer, chemoradiation, intensity-modulated radiotherapy, paclitaxel
Brief summary
The purpose of this study is to determine whether the combination of paclitaxel, capecitabine, mitomycin and intensity-modulated radiotherapy is more effective than the standard combination of capecitabine, mitomycin and intensity-modulated radiotherapy (IMRT) in patients with squamous-cell anal cancer.
Detailed description
This trial aims to investigate the efficacy of chemoradiotherapy with or without paclitaxel in squamous-cell anal cancer. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either standard IMRT with capecitabine and mitomycin or IMRT with capecitabine, mitomycin and paclitaxel. A stratification will be performed based on T stage, N stage and clinical center. Doses of capecitabine and mitomycin in experimental group were reduced for better treatment tolerance. The target accrual is 157 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 15% 3-yr disease-free survival (70% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging and followup. Pelvic MRI and histological diagnosis are subject to central review. Conduction of this study and data collection are controlled by a local institutional board.
Interventions
DRUGPaclitaxel
45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.
DRUGCapecitabine
625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
DRUGMitomycins
10 mg/m2, IV, on day 1. Number of infusions: 1.
RADIATIONRadiotherapy
Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage
Sponsors
Blokhin's Russian Cancer Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent * Histologically verified squamous-cell anal cancer * Stage I-IIIB (Union for International Cancer Control (UICC) TNM classification v7) * Eastern Cooperative Oncology Group (ECOG) status 0-2 * HIV (Human Immunodeficiency Virus) negative * Haemoglobin (HGB) \> 90 g/L * Platelet Count (PLT) \> 120x10\*9/L * Serum creatinine \< 150 µmol/L * Total bilirubin \< 25 µmol/L
Exclusion criteria
* inability to obtain informed consent * distant metastases * synchronous or metachronous tumors * previous chemotherapy or radiotherapy * clinically significant cardiovascular disorders (myocardial infarction \< 6 months before visit, stroke \< \< 6 months before visit, instable angina \< 3 months before visit, arrhythmia, uncontrolled hypertension \> 160/100 mm hg * clinically significant neurological disorders * previous neuropathy 2 or higher * current infection or heavy systemic disease * pregnancy, breastfeeding * ulcerative colitis * individual intolerance to treatment components * proven dihydropyrimidine dehydrogenase (DPD) deficiency * participation in other clinical trials * psychiatric disorders, which render patient unable to follow instructions or understand his/her condition * technical inability to perform pelvic MRI * inability of long-term followup of the patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 3-year disease-free survival | 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response at 26 weeks | 26 weeks | — |
| 3-year colostomy-free survival | 3 years | — |
| 3-year cancer-specific survival | 3 years | — |
| Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0 | 30 days | Toxicity measured according to NCI-CTCAE v.4.0 |
| Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria | 3 years | Late toxicity measured according to RTOG criteria |
| 3-year overall survival | 3 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life according to European organization for research and treatment of cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 (v.3) scale | 3 years | Change from baseline in quality of life on the EORTC QLQ-C30 (v.3) scale |
Outcome results
None listed