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

Blokhin's Russian Cancer Research Center

Status and phase: Unknown; Phase 3

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

Treatments: Drug: Mitomycins; Drug: Paclitaxel; Drug: Capecitabine; Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02526953

SCAC-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 314 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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314 participants in 2 patient groups

Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Mitomycins

Drug: Capecitabine

Drug: Mitomycins

Drug: Paclitaxel

Radiation: Radiotherapy

Drug: Capecitabine

Standard

Active Comparator group

Description:

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.

Treatment:

Drug: Mitomycins

Drug: Capecitabine

Drug: Mitomycins

Radiation: Radiotherapy

Drug: Capecitabine