Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer

Conditions
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Anus Neoplasms, Carcinoma, Squamous Cell, Anus Diseases, Neoplasms, Neoplasms, Squamous Cell, Carcinoma

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Capecitabine
* Drug: Capecitabine
* Drug: Mitomycins
* Drug: Mitomycins
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel<br>Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1. | Drug: Paclitaxel<br>* 45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.<br>* Other names: (2α,4α,5β,7β,10β,13α)-4,10-bis(acetyloxy)-13-{[(2R,3S)- 3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}- 1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate;Drug: Capecitabine<br>* 625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)<br>* Other names: Xeloda;Drug: Mitomycins<br>* 10 mg/m2, IV, on day 1. Number of infusions: 1.<br>* Other names: MMC;Radiation: Radiotherapy<br>* Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage<br>|
| Active Comparator: Standard<br>Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1. | Drug: Capecitabine<br>* 825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)<br>* Other names: Xeloda;Drug: Mitomycins<br>* 12 mg/m2, IV, on day 1. Number of infusions: 1.<br>* Other names: MMC;Radiation: Radiotherapy<br>* Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response at 26 weeks |  | 26 weeks | 
| 3-year colostomy-free survival |  | 3 years | 
| 3-year cancer-specific survival |  | 3 years | 
| 3-year overall survival |  | 3 years | 
| Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0 | Toxicity measured according to NCI-CTCAE v.4.0 | 30 days | 
| Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria | Late toxicity measured according to RTOG criteria | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anal cancer, chemoradiation, intensity-modulated radiotherapy, paclitaxel