Clinical trial NCT02526953: Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients
Official title: Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Anus Neoplasms
Carcinoma, Squamous Cell
Anus Diseases
Neoplasms
Neoplasms, Squamous Cell
Carcinoma
Keywords: anal cancer
chemoradiation
intensity-modulated radiotherapy
paclitaxel
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2015-08-18
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 3-year disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Complete response at 26 weeks
timeFrame: 26 weeks
measure: 3-year colostomy-free survival
timeFrame: 3 years
measure: 3-year cancer-specific survival
timeFrame: 3 years
measure: 3-year overall survival
timeFrame: 3 years
measure: Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0
timeFrame: 30 days
measure: Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria
timeFrame: 3 years
Other outcomes:
measure: Quality of life according to European organization for research and treatment of cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 (v.3) scale
timeFrame: 3 years
Locations:
Study officials:
affiliation: N.N.Blokhin Russian Cancer Research Center
name: Arsen O Rasulov, PhD
role: STUDY_CHAIR
References: